bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell‐mediated cytotoxicity to chemically‐induced rat tumours
Authors: Zöller Margot , Price Michael R. , Baldwin Robert W.
Published: February 2007

Cell‐mediated immune reactions against carcinogen‐induced rat tumours were demonstrated by the in vitro microcytotoxicity test. Lymph‐node cells from syngeneic rats immunized against individual aminoazo‐dye‐induced hepatomas or 3‐methylchol‐anthrene‐induced sarcomas were cytotoxic for cells of the immunizing tumour compared with the effects of normal lymph‐node cells. Only a low level of cross‐reactivity was detectable against target cells derived from other tumours. Conversely, lymph‐node cells from tumour‐bearing rats were cross‐reactive against a range of tumour cells, suggesting that the tumour‐bearer was sensitized against a common antigen (s) as well as the individually specific antigen associated with these tumours. Lymph‐node cells were reactive at an early time (from day 2) after tumour implantation and their cytotoxic potential persisted until terminal stages of tumour growth. Spleen cells from tumour‐bearer and tumour‐immune donors also exhibited comparable cytotoxic reactivities of the same specificity as that shown by lymph‐node cell preparations. These findings are discussed in relation to the development of cell‐mediated immune responses in the tumour‐bearing rat and in immunized rats which are capable of rejecting transplanted tumour cells.
Early onset of serum blocking in a murine melanoma model
Authors: Bray Alan E. , Holt Patrick G. , Roberts Lynne M. , Keast David
Published: February 2007

The early onset of serum blocking of host cell‐mediated immunity was investigated in a transplantable murine melanoma model employing two in vitro assays. One of these was based on the Takasugi and Klein cytotoxicity test; the other was a new test based on the inhibition of adherence of leukocytes to a plastic surface in the presence of tumor antigen. Both tests yielded similar results, and the adherence inhibition test was more sensitive. Blocking could be detected as early as 1 h after the inoculation of 1×107 melanoma cells. Early onset of serum blocking was also demonstrable if homogenized or tissue‐cultured tumor cells were inoculated. Serum blocking under these circumstances was initially transient, declining at 24 to 48 h, but reappearing by the 4th day after inoculation. Furthermore, a functional immune system was not required for blocking factor development in this system, as evidenced by the onset of a similar pattern of blocking activity in heavily irradiated animals.
The relationship between tumorigenicity, growth in agar and fibrinolytic activity in a line of human osteosarcoma cells
Authors: Jones Peter A. , Rhim Johng S. , Isaacs Hart , McAllister Robert M.
Published: February 2007

The TE‐85 osteosarcoma cell line has several of the in vitro properties of malignant cells, including colony formation in agar, but has low extracellular fibrinolytic activity and no capacity to form tumors in ATS‐treated hamsters. Some TE‐85 cell clones (clones 2, 4 and 6) have increased fibrinolytic activity but do not form tumors in hamsters. TE‐85 cells infected with mammalian transformation‐defective viruses have low (FeLV) or increased (RD‐114 virus) levels of fibrinolytic activity and do not form tumors in hamsters. TE‐85 cells either nonproductively infected with Ki‐MSV or productively infected with M‐MSV (RD‐114), have fibrinolytic activity and can form tumors in hamsters. The MSV gene(s) but not colony formation in agar or extracellular fibrinolytic activity appears to be capable of rendering TE‐85 cells tumorigenic in ATS‐treated hamsters.
Strain‐dependent expression of endogenous mouse‐tropic leukemia viruses in chemically induced murine leukemias
Authors: Odaka Takeshi
Published: February 2007

The effects of two chemical carcinogens, nitrosobutylurea and 7,12‐dimethylbenz‐(a)anthracene, on the expression of endogenous N‐ and B‐tropic viruses were studied. The mice used were from two inbred strains, C57BL/6 and DDD‐FVr, and from 13 partially inbred strains derived from the cross of C57BL/6 with DDD‐FVr. These mouse strains are classified into three groups by the pattern of expression of endogenous viruses in normal, aged mice: (1) negative for both viruses; (2) positive for N‐tropic virus only; and (3) positive for both viruses. Mice were given the carcinogens, and were tested at various intervals by the UV‐XC procedure for the viruses in the spleens and other enlarged organs. Irrespective of the presence or absence of leukemias, the carcinogen‐treated mice showed the same pattern of expression of endogenous viruses as that of non‐treated normal mice. It can be concluded that the activation of the endogenous viruses is dependent on the mouse strains and that the growth of the activated viruses is not a necessary step for the chemical induction of leukemias.
Activation of “eclipsed” lymphoid cells from advanced tumor‐bearing mice through adoptive transfer to sublethally irradiated syngeneic hosts
Authors: Youn J. K. , Le Francois D. , Hue G. , Santillana M. , Barski G.
Published: February 2007

Immunologically inactive or “eclipsed” lymphoid cells from advanced tumor‐bearing mice were investigated following their adoptive transfer to irradiated syngeneic hosts. Experiments were performed with two syngeneic tumor‐host systems: the T5‐BALB/c tumor line chronically infected with a low‐leukemogenic Rauscher virus variant and the TM1‐C3H tumor line developed from a spontaneous C3H/He mouse mammary tumor. In confirmation of our previous data, peritoneal cells (PC) from advanced tumor‐bearing mice (EPC) appeared to have lost any capacity to inhibit specifically the growth of corresponding tumor target cells in in vitro colony inhibition (CI) tests, whereas PC from immunized mice (IPC) were perfectly active. When these EPC were adoptively transferred by intraperitoneal inoculation into sublethally irradiated (450R) syngeneic mice in association with respective tumor extracts (TE), the PC from such recipient mice, taken 5 to 13 days later, were nearly as active in in vitro CI tests as were PC from parallel IPC‐recipient mice. For this recovery of specific immunological activity following the adoptive transfer of EPC the adjunction of the TE and irradiation of the recipient animals seem important and may be necessary. On the other hand, no specific immunological activity was seen in PC from irradiated mice to which PC from normal mice had been transferred with TE. In addition to the in vitro results, an effect of adoptive transfer of EPC (retardation of tumor growth) was also observed in vivo. It is concluded that the “eclipsed” immunologically inactive state of the EPC in mice bearing advanced tumor is not irreversible and that activation of these cells can occur in vivo under certain conditions helped by the presence of tumor‐specific antigenic stimulus.
Mutation induction in chinese hamster V79 cells by two vinyl chloride metabolites, chloroethylene oxide and 2‐chloroacetaldehyde
Authors: Huberman Eliezer , Bartsch Helmut , Sachs Leo
Published: February 2007

Chloroethylene oxide and 2‐chloroacetaldehyde, two possibly carcinogenic metabolites of vinyl chloride in mammals, caused a dose‐dependent induction of 8‐azaguanine‐and ouabain‐resistant mutants in Chinese hamster V79 cells in vitro. Up to one‐hundredfold higher concentrations of 2‐chloroethanol or monochloroacetic acid, a urinary vinyl chloride metabolite in rats and man, were inactive.
A long‐term 51chromium assay for in vitro cell‐mediated tumor immunity. Correlation with simultaneously performed microplate assays
Authors: Steele Glenn , Sjögren H. O. , Lannerstad O. , Stadenberg I.
Published: February 2007

In vitro assays of cell‐mediated tumor immunity utilizing 51Chromium (51Cr) labelling of cultured adherent solid tumor cells were designed which allowed an effector cell/target cell incubation time of 48 h without overriding spontaneous 51Cr release. In a series of 16 consecutive experiments, blood lymphocytes from healthy human donors, from patients with tumors unrelated to the cultured tumor target cells, and from colon carcinoma and melanoma patients were tested for their cytotoxic effects on various target cell pairs, human colon carcinoma, melanoma, or skin fibroblasts. The same reagents were used in simultaneously performed microplate and 51Cr assays. Results obtained by visual counting of microplate tests and by 24‐h assays of 51Cr release or 51Cr retention correlated in 20/25 effector‐cell/target‐cell combinations. In a series of six consecutive experiments, lymph‐node cells from untreated Wistar/Furth rats, and rats bearing either chemically‐induced colon carcinoma NG‐W1 or polyoma virus‐induced sarcoma P‐W13 were tested for their cytotoxicity on syngeneic rat colon carcinoma and sarcoma target cells. Criss‐cross type experiments were performed by microplate and 51Cr techniques done in parallel. Results obtained by visual counting of microplate tests and by 48 h assays of 51Cr release or 51Cr retention correlated in 15/18 effector‐cell/target‐cell combinations.
Nasopharyngeal carcinoma. IX. Antibodies to EBNA and correlation with response to other EBV antigens in Chinese patients
Authors: De‐Thé G. , Ho J. H. C. , Ablashi D. V. , Day N. E. , Macario A. J. L. , Martin‐Berthelon M. Cl. , Pearson G. , Sohier R.
Published: February 2007

Ninety‐five sera from Chinese NPC patients in different stages of the disease, 38 sera from Chinese patients with other cancers, and 50 normal Chinese sera, were titrated for EBNA, VCA, EA and complement‐fixing (CF/S) EBV‐specific antibodies. The geometric mean (GMT) EBNA antibody titre of patients with NPC at stage I was found to be four times higher than that of normal individuals and increased in parallel with clinical deterioration. Antibody titres against EBNA did not correlate with either VCA or EA antibodies but, in general, correlated with CF/S antibodies. EA antibodies correlated relatively well with VCA antibodies and discriminated better than EBNA titre between NPC at stage I and controls.
Humoral cytotoxicity in melanoma patients and its correlation with the extent and course of the disease
Authors: Canevari Silvana , Fossati Giuseppe , Della Porta Giuseppe , Balzarini Gian Paolo
Published: February 2007

Complement‐dependent cytotoxicity against melanoma cells was demonstrated with a microassay in sera from melanoma patients. The response was tumor‐specific and histologic type‐specific since 16 out of 52 (30%) melanoma patient sera taken before surgery reacted against melanoma cells, whereas 3 out of 43 (7%) control sera, collected from patients with unrelated tumors and from cancer‐free individuals, were positive. The serum activity correlated with the clinical stage of the disease since it was detected in 15 out of 40 patients with stage I and II tumors and in 1 of the 12 patients in stage III. Twelve melanoma patients, clinically tumor‐free for 1 to 4 years after surgery, showed no humoral cytotoxicity. A follow‐up study of 13 melanoma patients revealed that the cytotoxicity appeared 7‐10 days after radical removal of the tumor and that it disappeared if there was no recurrence. The histologic type‐specificity was further tested by assaying sera from 16 melanoma and 10 breast‐cancer patients simultaneously on both melanoma and breast‐cancer cells; a positive reaction was observed in 6 cases of melanoma and in 5 of breast cancer on homologous cells only, in 1 case on the opposite type of cells, and in 3 cases on both types of tumor cells.
Alien histocompatibility determinants on the cell surface of sarcomas induced by methylcholanthrene. I. In vivo studies
Authors: Parmiani Giorgio , Invernizzi Giovanni
Published: February 2007

Groups of BALB/c mice were immunized to normal tissues (skin and/or liver plus kidney) of C3Hf, C57BI/6, DBA/2 and AKR strains and challenged with either of two syngeneic 3‐methylcholanthrene‐induced immunogenic sarcomas, ST2 and TZ15, or with a “spontaneous” non‐immunogenic BALB/c sarcoma, B2. It was found that anti‐C3Hfand anti‐DBA/2 immune mice were significantly protected against the growth of ST2, whereas anti‐AKR immune mice rejected TZ15; no protection was elicited by immunizing with normal tissues of any strain against B2, which lacked individual tumorassociated transplantation antigens (TATA). The reciprocal experiment, i.e. the immunization of BALB/c mice with tumor cells and challenge with skin grafts of different strains, was also carried out with ST2 and TZ15. Accelerated rejection of all the various allogeneic skins was observed in anti‐ST2 immune mice and of AKR and C3Hf skin in anti‐TZ15 immune animals. In addition the Winn test demonstrated that lymph‐node cells of BALB/c mice immune to C3Hf or DBA/2 tissues were specifically inhibitory for ST2, and that lymph‐node cells immune to AKR tissues protected against TZ15. In a further experiment both ST2 and TZ15 tumors were left to grow in (C3Hfx BALB/c)F1, (C57BI/6 × BALB/c)1, (BALB/c × DBA/2)F1 and (BALB/c × AKR)F1 mice; the tumors were then excised and the “immune” mice challenged with the related tumor to measure their immune response in comparison with that elicited by the same procedure in BALB/c mice. ST2 was highly immunogenic in syngeneic BALB/c mice and in all the hybrid combinations except (C3Hfx BALB/c)F1 mice, where it completely lost its immunogenicity; TZ15 showed a certain loss of immunogenic strength in (BALB/c × AKR)F1 hybrids. It was concluded that TATA of ST2 contain antigenic determinants expressed on the normal cells of C3Hf and DBA/2 strains, and that TATA of TZ15 are likely to share antigens with AKR normal tissues.
The effect produced by some carcinogenic nitrosocompounds on organ cultures from human embryonic lung and kidney tissues
Authors: Shabad L. M. , Kolesnichenko T. S. , Golub N. I.
Published: February 2007

Previous works using organ cultures of lung and kidney tissues of mouse, rat and hamster embryos exposed to transplacental action of some carcinogens showed premalignant growth. This paper presents the results of organ culture of human embryonic lung and kidney tissues. Direct action of some carcinogenic nitrosocompounds (N‐nitrosomethylurea, dimethylnitrosamine and orthoaminoazotoluene) resulted in higher survival of the treated organ cultures and induced epithelial hyperplasia. The changes depended directly upon the dose of carcinogen employed.
Epoxides metabolically produced from some known carcinogens and from some clinically used drugs. I. Differences in mutagenicity
Authors: Glatt H. R. , Oesch F. , Frigerio A. , Garattini S.
Published: February 2007

The epoxide metabolites of two clinically used drugs and an experimental psychotropic agent, carbamazepine 10,11‐oxide, cyproheptadine 10,11‐oxide and cyclobenzaprine 10,11‐oxide, were fully devoid of any mutagenic activity under conditions where K‐region‐epoxide metabolites of some known carcinogens, such as benzo (a)pyrene, proved to be potent frameshift mutational agents for Salmonella typhimurium TA 1537 and TA 1538. All epoxides tested were non‐mutagenic for TA 1535, designed to detect substitution mutations. The 10,11‐epoxides of the three drugs, carbamazepine, cyproheptadine and cyclobenzaprine, were not cytotoxic to any of the bacterial tester strains used, precluding that mutagenicity might have been overshadowed by cytotoxicity. When the mutagen precursor, benzo (a)pyrene, was incubated together with TA 1537 and a mammalian microsomal preparation in the presence of a system generating the co‐factor necessary for mono‐oxygenase activity, activation to mutagenic species was observed which was dramatically increased in the presence of a potent epoxide hydratase inhibitor, 1,1,1‐trichloropropene 2,3‐oxide, suggesting epoxide (s) as the (or one of the) mutagenically active species metabolically produced in situ. None of these effects was observed with the three medical drugs. Moreover, the observation that the alkene oxide 4‐phenylstyrene 7,8‐oxide is mutagenic to the two strains TA 1537 and TA 1538 but the K‐region arene oxide derived from 7,12‐dimethylbenz (a) anthracene is inactive for the latter strain indicates that epoxidation of an aromatic double bond of a polycyclic hydrocarbon is neither a necessary nor a satisfying condition for frameshift mutagenesis to occur.
Host responses within solid tumors: Non‐thymus‐derived specific cytotoxic cells within a murine mammary adenocarcinoma
Authors: Haskill J. Stephen , Yamamura Y. , Radov L.
Published: February 2007

The nature of host‐derived, specifically cytotoxic cells infiltrating solid murine mammary adenocarcinomas (line T1699) was investigated. Cell suspensions obtained from enzymatically dispersed tumors were separated by sedimentation velocity. The host cell fraction was heterogeneous and contained T‐lymphocytes, non‐phagocytic cells bearing Fc receptors, eosinophils and monocytes. Host cells equivalent in size to small lymphocytes and bearing Fc receptors were found to be the predominant cell type responsible for colony inhibition. These colony‐inhibiting cells were insensitive to lysis with either anti‐θ or anti‐IgG serum and complement; and they were specific both in their induction and in their mediation of cytotoxicity. Host cells made up the predominant population in spontaneously regressive tumors but only a minor component in progressive tumors, and they were totally absent from progressive tumors in X‐irradiated animals.
Preneoplastic changes in rabbit pancreatic duct cells produced by dimethylhydrazine
Authors: Elkort R. J. , Handler A. H. , Mozden P. J.
Published: February 2007

Permeation catheters containing 40% dimethylhydrazine (DMH) were implanted into the main pancreatic duct of New Zealand white rabbits. The catheters were constructed of silicone polycarbonate with a 4‐ to 10‐day carcinogen release rate. Rabbits implanted with catheters containing DMH showed pancreatic ductal cell hyperplasia, metaplasia and dysplasia with periductal cell infiltration, adenosis and adenoma formation. These changes began approximately 9 to 12 weeks after implantation and persisted for 75 to 80 weeks. Specificity of the delivery system appeared to be excellent in that pathologic effects were observed only in the pancreatic and peripancreatic tissues. Moreover, these effects were probably directly related to the implanted carcinogen since similar maintained effects were not observed in control animals.
A quantitative comparison between in vivo‐and in vitro‐derived friend leukemia virus
Authors: Evenson Donald P. , Pla Dolores M. , Beju Delia , De Harven Etienne
Published: February 2007

The biological activities of RNA viruses derived from Friend leukemia cells in culture (TCV) were compared with those of viruses derived from the plasma (PV) of mice infected with Friend leukemia virus (FLV). The comparison was quantitatively based on the actual number of viruses used in each experiment as determined by counting under the electron microscope. Electron microscopy also provided a qualitative assessment of the structural integrity of the concentrated virus particles used in various bioassays. The data show that the leukemogenic and spleen‐focus‐forming (SFF) activities of TCV, although demonstrable, are respectively 105 and 104 lower than those of PV. Moreover, TCV has 104 less helper activity (S+L− test) than PV. The level of reverse transcriptase activity is ten times lower in TCV than in PV which indicates that there is little correlation between polymerase activity and the other biological activities measured. The decreased biological activity of the in vitro grown virus is thought to be intrinsic to this type of virus although all extrinsic factors have not been ruled out.
Characterization of non‐producer human cells induced by kirsten sarcoma virus
Authors: Rhim J. S. , Cho H. Y. , Vernon M. L. , Arnstein P. , Huebner R. J. , Gilden R. V. , Nelson‐Rees W. A.
Published: February 2007

Non‐producer (NP) human cells induced by the Kirsten sarcoma virus were characterized. These morphologically altered NP cells produced neither infectious virus nor complement‐fixing antigens of the murine sarcoma—leukemia virus complex. The NP cells did not release RNA‐dependent DNA polymerase and type‐C virus particles with a density of approximately 1.15 g/ml in sucrose gradients by 3H‐uridine labelling. The NP cells produced tumors when transplanted subcutaneously into athymic nude mice. The tumor cells re‐established in culture resembled the original NP cells, were confirmed as human cells by karyological analysis and were also found to be “nonproducer”. The sarcoma virus genome in NP cells could be rescued not only by co‐cultivation with “helper virus”‐releasing cells but also by superinfection with helper type‐C viruses. Murine (Rauscher, Ki‐MuLV, AT‐124 and two other xenotropic viruses), feline, RD‐114 and Simian (woolly monkey and baboon) type‐C viruses possessed the ability to rescue the sarcoma genome from NP cells but not AKR leukemia virus. In addition, the feline leukemia virus titer obtained by the rescuing technique in NP cells was the same as those obtained in feline embryo and NP cells by CF induction assay.
Specific responsiveness of leukocytes to soluble extracts of human tumors
Authors: Powell A. E. , Sloss A. M. , Smith R. N. , Makley J. T. , Hubay C. A.
Published: February 2007

The leukocyte adherence inhibition (LAI) method was studied with respect to its specificity in detecting responses to extracts of tumor tissues or normal lymphocytes. Responses of cells from normal persons were within 10% of each other whether incubation was carried out with culture medium alone or with any of the extracts. The same was true of cells from 78 cancer patients unless the cells were incubated with extracts of the same histologic type as their own. In the latter case, statistically significant responses occurred in 95% of the 110 analyses done. Negative responses were given by cells from 14 patients tentatively diagnosed as having breast carcinoma but whose lesions later proved benign. There was one positive response inconsistent with the diagnosis. Of 29 normal individuals known to have been exposed to tumors or tumor extracts, 11 responded positively and specifically to the relevant tumor extract. Cells from 12 of 30 multiparous female breast‐cancer patients responded to extracts of pooled normal lymphocytes. The results establish that the LAI analysis is an extremely specific means of detecting systemic responses to malignant diseases. In addition, analyses have proven positive in 95% of the cases studied.
Some electrical properties of the peripheries of murine 3T3 cells with respect to viral transformation and reversion
Authors: Weiss L. , Subjeck J. R. , Poste G.
Published: February 2007

Mouse 3T3, Simian virus 40 transformed 3T3 cells (SV3T3) and two SV3T3 lines showing reversion of their transformed phenotype (Rev 3 and Rev 5) have been studied with respect to electrophoretic mobilities and colloidal iron hydroxide (CIH) binding density visible by electron microscopy, before and after incubation with neuraminidase or ribonuclease. The results show that, in general, the marked changes in both sets of surface parameters associated with transformation are largely reversed in the Rev 5 revertant, and only partially reversed in the Rev 3 line. It was also observed that, in common with Ehrlich ascites tumor (EAT) cells examined previously, the densities of CIH‐particles bound over the microvilli of all the cell types was 1.5 to 2.7 times higher than those bound to the spaces between them. In contrast to the EAT cells, the higher density of CIH particles bound over the microvilli was not due to neuraminidase‐sensitive binding sites.
Studies of genetic transmission of mammary tumour virus by C3Hf mice
Authors: Van Nie R. , Verstraeten A. A.
Published: February 2007

By radioimmunoassay (RIA) mammary tumour virus (MTV) antigens were detected in individual milk samples of C3Hf mice, (♀BALB/c × ♂ C3Hf)Fl mice and (♀C3Hf × ♂ BALB/c)Fl mice; milk samples of BALB/c mice were negative. In the segregating backcross I population, ♀ BALB/c × ♂ (♀BALB/c × ♀ C3Hf) viral antigens were found in the milk of 93 out of 169 mice (55%). In the Bc II population (daughters of Bc I mothers and BALB/c fathers) two groups were distinguished. In the first group, derived from positive Bc I mothers, 55 out of 110 mice (50%) had detectable levels of viral antigens in the milk. In the second group, progeny of negative Bc I mothers, 1 mouse out of 47 was positive. These data are consistent with the assumption that one dominant gene is responsible for the presence of viral antigens in the milk of C3Hf mice. This gene (Mtv‐1) seems to be linked with the albino locus situated on chromosome 7; the recombination percentage was about 29. In the first experiment with Bc I mice a significant difference was found between the tumour ages of the mice with virus‐positive milk and of the mice with virus‐negative milk: all mice (18) with viral antigens in the milk developed mammary tumours at an age ranging from 7 to 18 months, whereas in only 7 out of 16 mice with virus‐negative milk were mammary tumours found before the age of 21 months. Viral antigens were detectable (by RIA) in the tumours of mice of both subgroups; however, the amounts (mU/mg tumour) were significantly lower in the tumours derived from mice with virus‐negative milk. Although MTV‐L of C3Hf mothers could be transmitted to BALB/c mice by foster‐nursing, viral antigens could not be detected in milk samples collected prior to the third lactation period; thus an influence on the data of extrachromosomally transmitted MTV‐L is unlikely.
In vitro synthesis of tumor‐specific factors with blocking and antibody‐dependent cellular cytotoxicity (ADC) activities
Authors: Nelson Karen , Pollack Sylvia B. , Hellström Karl Erik
Published: February 2007

Spleen cells from BALB/c mice bearing syngeneic sarcomas and from BALB/c mice whose sarcomas had been excised were cultivated in vitro. The culture supernatants were tested for two activities: their ability (1) to suppress (“block”) specific lymph‐node cell‐mediated cytotoxic reactions directed against the respective neoplasms; and (2) to induce antibody‐dependent cellular cytotoxicity (ADC) specific for the antigens of the respective tumors. Both specific activities, blocking and induction of ADC, were detected in culture supernatants from spleens of tumor‐bearing mice, even when repeatedly harvested at intervals over a 7‐day period. Supernatants of cultured spleen cells from mice whose sarcomas had been excised 3‐4 weeks previously also had ADC but no blocking activity. Supernatants of cultures treated with inhibitors of protein synthesis lacked both blocking and ADC activities; the inhibitory effect of cycloheximide on these activities, as well as on protein synthesis, was reversible. Factors in the culture supernatants responsible for blocking and for ADC were labelled when the culture were incubated with 14C‐leucine. The labelled material was retained by, and could be eluted from, immunoadsorbents for mouse immunoglobulins. In addition, the labelled material bound preferentially to those tumor cells for which specific blocking or ADC activities were observed. The findings indicate that factors responsible for the blocking and ADC phenomena were indeed synthesized by the spleen cells in vitro.
Antigenic specificities of the cell‐mediated anti‐tumor reactions in the MSV system studied by the secondary chromium release test
Authors: Senik A. , Gisselbrecht S. , Levy J. P.
Published: February 2007

The SCRT and the inhibition test have been used to determine the specificity of cell surface antigens reacting with anti‐M‐MSV cytolytic lymphocytes. The method provides very sensitive and specific results. Some discrepancies exist between the results of SCRT and those obtained by the in vitro inhibition by tumor cells of cell‐mediated immune cytolysis. The main point is that allogeneic cells are stimulatory in SCRT, whereas they are not reactive in the inhibition test. Several hypotheses are discussed to explain these discrepancies. In all the experiments, a strong secondary stimulation of cytotoxic lymphocytes was obtained in vitro when FMRGi (+) cells were used as stimulators, whatever the nature and the histocompatibility antigens of these cells. This suggests that an antigen of the “FMRGi system” is regularly involved in the cell‐mediated anti‐MSV reaction. However, other antigenic specificities of different natures are probably also concerned due to the antigenic complexity of these tumors.
Detection of virus‐specific DNA and RNA base‐sequences in individual cells transformed or infected by adenovirus type 2
Authors: Moar M. H. , Jones K. W.
Published: February 2007

By means of 3H thymidine‐labelled adenovirus 2 DNA, adenovirus‐specific DNA sequences have been localized in individual nuclei of adenovirus 2‐ or 12‐infected cells, and adenovirus‐specific RNA sequences have been detected in the permissive cells as well as in cells transformed by adenovirus type 2. The ability to detect such specific virus RNA base‐sequences in particular, by in situ hybridization, should be useful in studying the transcriptional specificities of tumours and neoplasms.
Origin of lymphoid lines established from mixed cultures of cord‐blood lymphocytes and explants from infectious mononucleosis, burkitt lymphoma and healthy donors
Authors: Dalens M. , Zech L. , Klein G.
Published: February 2007

Lymphocytes were explanted from EBV‐seropositive donors including peripheral blood of infectious mononucleosis patients, healthy donors and EBV‐genome‐carrying cells from Burkitt lymphoma (BL) biopsies or nude mouse‐passaged, BL‐biopsy‐derived lines. The explanted cells were mixed with fresh cord‐blood lymphocytes from mice of the opposite sex. In all categories of derived lines, cord‐blood cell progeny was predominant, as judged by the sex marker and other associated markers. Only one BL biopsy line, serially passaged in nude mice, gave rise to a monoclonal lymphoma line.
Inhibition of leukocyte migration in agarose by KC1 extracts of a human melanoma cell line grown in serum‐free medium
Authors: Boddie A. W. , Urist Marshall M. , Chee Darwin O. , Holmes E. Carmack , Morton Donald L.
Published: February 2007

KCl extracts of Melanoma 14, a human melanoma cell line grown in chemically defined serum‐free medium, inhibited leukocyte migration in 19/36 (53%) patients with malignant melanoma. Only 4/23 (17%) controls with non‐melanoma malignancies and 4/28 (14%) normal subjects with no history of cancer were similarly inhibited. Only 2/27 melanoma patients tested against KCl extracts of normal muscle tissue excised from the donor of Melanoma 14 were significantly inhibited. Patients with Stage I (localized) melanoma and patients with Stage III (generalized) melanoma reacted with roughly equal frequency but the number of patients in each group was too small for meaningful statistical analysis. Leukocytes from the donor of Melanoma 14 were tested in a completely autologous system against extracts of Melanoma 14 tissue culture cells and extracts of autologous muscle and were specifically inhibited by the Melanoma 14 tissue culture extract (Migration Index = 0.67) but not by the extract of normal muscle (Migration Index = 0.96). Only 7/32 (22%) melanoma patients were significantly inhibited by an extract of non‐melanoma tumor. These results suggest that melanoma‐associated antigens are present in soluble extracts of this tumor line. Such extracts could provide a continuing source of standard melanoma‐associated antigens for purification and chemical characterization and for diagnostic and prognostic tests in patients with malignant melanoma.
Comparison between two antibody populations in the EBV system: Anti‐MA Versus neutralizing antibody activity
Authors: De Schryver André , Rosén Anders , Gunvén Peter , Klein George
Published: February 2007

EBV‐neutralizing antibody titers were determined in 11 sera derived from African Burkitt lymphoma or nasopharyngeal carcinoma patients and in the corresponding serum fractions retained above XM 100 Diaflo membranes after low pH treatment, and after recombination of the retained and passed fractions by neutralization of the acidified samples. They were compared with the corresponding antimembrane antigen (MA) titers in seven of the same sera. While all sera tested showed substantial increase of the anti‐MA activity in the retained fraction, resulting in a significantly increased mean titer, EBV neutralizing activity did not change at all after identical treatment or changed only in a random fashion, resulting in stable mean titers. It is suggested that anti‐MA and neutralizing antibodies are directed against at least partly different antigens on the virus.
In vitro cell‐mediated immune reactions of melanoma and colorectal carcinoma patients demonstrated by long‐term 51chromium assays
Authors: Steele Glenn , Sjögren H. O. , Standenberg I.
Published: February 2007

In a series of consecutive 51chromium (51Cr) assays, 21 melanoma and 14 colo‐rectal carcinoma patients were tested for their in vitro cell‐mediated immune reactions to melanoma, rectal adenocarcinoma, and normal fibroblast target cells. Blood lymphocytes (BL) from four individuals were included in each experiment. In 9/14 experiments the BL effects of 2 melanoma patients were compared to BL effects of 2 colorectal carcinoma patients. In two experiments, BL from 1 melanoma patient and 1 colorectal carcinoma patient were compared for cytotoxic effect with each other and with BL from 2 normal healthy donors, and in the remaining 3 experiments BL from 2 melanoma patients were compared with BL from 1 healthy donor and one patient bearing a tumor which was neither a melanoma nor a colorectal carcinoma. Eleven out of 14 experiments were performed in a criss‐cross manner. Target cells in the first three tests of this series consisted of tumor cells and fibroblasts explanted from a single melanoma patient. In all of the remaining experiments, each BL population was tested for cytotoxicity against both a tumor‐fibroblast target cell pair explanted from one of two melanoma patients and a tumor‐fibroblast target cell pair explanted from a rectal adencarcinoma patient. Out of 35 tumor patients, 27 (77%) demonstrated a selective cytotoxic effect on the tumor target cells compared to the corresponding fibroblasts, while 4 patients (11%) showed a selective effect on the fibroblasts and 6/29 patients showed a selective effect on the other type of tumor cells compared to matching fibroblasts. In 8/11 experiments (including two repeat tests) tumor‐specific BL effects were demonstrated in a criss‐cross manner. BL effects were demonstrated in a criss‐cross manner. BL separations and 51Cr tests were repeated in 11 of the 35 patients 2‐4 weeks after their original tests. BL populations from these 11 patients reproduced their individual earlier effects, whether these effects showed specific, non‐specific, or no cytotoxicity. In each assay, differences in sensitivity between fibroblasts and tumor target cells in matched pairs were analyzed by comparing the effects of BL from the two controls. No differences in target‐cell sensitivity could be demonstrated.
Different surface glycoprotein patterns on human T‐, B‐ and leukemic‐lymphocytes
Authors: Andersson Lief C. , Wasastjerna Curt , Gahmberg Carl G.
Published: February 2007

We have labeled the exposed surface glycoprotein of human blood T‐ and B‐lymphocytes and cells from patients with chronic lymphocytic leukemia by the galactose oxidase‐tritiated sodium borohydride method. The labeled glycoproteins were separated by polyacrylamide slab gel electrophoresis and visualized by autoradiography. The T‐ and B‐lymphocytes show different and characteristic surface glycoprotein patterns. The surface glcoprotein patterns of the leukemic cells differ from those of normal, non‐malignant lymphocytes. A relationship between the altered surface glycoprotein pattern of leukemic cells and the expression of leumemiaassociated antigens is discussed.
Viral “Tumorigenesis” in man: Cell markers in condylomata acuminata
Authors: Friedman J. M. , Fialkow Philip J.
Published: February 2007

Determination of the glucose‐6‐phosphate dehydrogenase (G‐6‐PD) phenotype of a neoplasm occurring in a heterozygous female can be used to trace the cellular origin of the tumor. This technique was performed on 834 individual verrucous subunits from four condylomata acuminata (venereal warts) arising in two patients heterozygous for a B and an A gene at the G‐6‐PD locus. All four specimens contained both A and B types of G‐6‐PD. Furthermore, even single verrucous subunits from each specimen occasionally contained both enzyme types. These data indicate that condylomata acuminata have a multicellular origin. The initial number of cells which, after viral infection, developed into a condyloma acuminatum was estimated to be about 4,400 cells, on the basis of statistical analysis of the data in one case.
A continuous tumor‐cell line from a human lung carcinoma with properties of type II alveolar epithelial cells
Authors: Lieber Michael , Todaro George , Smith Barry , Szakal Andras , Nelson‐Rees Walter
Published: February 2007

The A549 tumor‐cell line, initiated from a human alveolar cell carcinoma, has been continuously propagated in vitro for more than 3 years (more than 1,000 cell generations). These cells have a human karyotype and appear to have been derived from a single parent cell. All A549 cells examined by electron microscopy at both early and late passage levels contain multilamellar cytoplasmic inclusion bodies typical of those found in type II alveolar epithelial cells of the lung. At early and late passage levels, the cells synthesize lecithin with a high percentage of disaturated fatty acids utilizing the cytidine diphosphocholine pathway; such a pattern of phospholipid synthesis is expected for cells believed to be responsible for pulmonary surfactant synthesis. The A549 cell line should permit in vitro analysis of human surfactant synthesis and secretion and possibly provide a source of human surfactant for therapeutic intervention in pulmonary disease states characterized by surfactant deficiency.
Tumor‐bound immunoglobulins. Evidence for the in vivo coating of tumor cells by potentially cytotoxic anti‐tumor antibodies
Authors: Ran Maya , Witz Isaac P. , Klein George
Published: February 2007

The experiments described herein were designed to determine whether part of the Ig coat of tumor cells consists of specific anti‐tumor antibodies. It was demonstrated that the inoculation of polyoma virus‐induced sarcoma cells (SEYF‐a) into syngeneic A.B Y mice stimulates the production of cytotoxic antibodies against the tumor‐cell population. The level of these antibodies, which was undetectable during the first week after transplantation, increased markedly during the second week, and remained high thereafter. Following the increase in cytotoxic antibodies in the serum, a cell‐bound potentially cytotoxic antibody was detected on the tumor cells by testing their sensitivity to rabbit complement. The increase in cell‐bound, potentially cytotoxic antibody followed the kinetics of the increase in serum antibody during the second week after transplantation and was inversely correlated to the amount of free antigens on the cell surface. These antigens, responsible for the sensitivity of the cells to a syngeneic hyperimmune cytotoxic antiserum, became non‐available for the cytotoxic antibodies during propagation of the tumor cells. Cells from a tumor propagated for 3 weeks could not compete for antitumor antibodies with cells propagated for 1 week. Yet it was possible to increases the antigenic capacity of cells from an old tumor by a treatment that would cause the release of tumor‐associated Ig. Cytotoxic anti‐SEYF‐a antibodies could be dissociated from tumor cells propagated in vivo by methods causing dissociation of antigen‐antibody complexes, and detected in tumor eluates.
Humoral immune responses of cats to mammalian type‐C virus p30s
Authors: Charman Howard P. , Kim Nancy , Gilden R. V. , Gardner Murray B. , McAllister Robert M.
Published: February 2007

Natural and expreimental cat sera were tested in radioimmune precipitation assays vs purified p30s from FeLV, RD114 and MuLV. Antibodies with specificity for FeLV p30 comparable to hyperimmune sera from heterologous species but of low titer were found in a high percentage of normal cats from households with a high incidence of FeLV and neoplasia. Sera from cats with neoplasms were generally negative. Cats immunized with FeLV gave low‐level immune response, also of the same general specificity as heterologous hyperimmune sera. Cat sera do not normally show antibody to RD114 p30 although two immunized weanling cats produced low titered but highly specific p30 antibody. Thus, for both classes of feline type‐C virus p30s, there is an evident capability of the cat to mount an immune response to naturural or experimental exposure to the respective proteins. The magnitude of the response is between 100 and 1,000 fold below that seen in heterologous species. In contrast, cats immunized with MuLV p30 gave immune responses comparable to those seen in guineapigs, rabbits and goats. Several very old cats with carcinoma had antibody which preferentially precipitated MuLV p30. A competition assay using one such serum and labelled MuLV p30 was inhibited by FeLV, RD114, and MuLV p30s. This indicates that the assay is “interspecies” in nature. Among the possible explanations of this reaction category is that it represents antibody to the p30 of an as yet undefined class of feline type‐C virus.
Biochemical changes during regression and regrowth of hormone‐dependent gr mouse mammary tumors
Authors: Schülein M. , Daehnfeldt J. L. , Briand P.
Published: February 2007

Discontinuation and recommencement of estrone‐progesterone treatment causes regression and regrowth, respectively, of transplantable hormonedependent GR mouse mammary tumors. This tumor model was found convenient for the demonstration of hormonal responses in hormone‐dependent mouse mammary tumor cells. Tumor regression was palpable 2 days after discontinuation of hormonal treatment and tumors reached half their size within 3‐6 days. At this point, hormones were readministered and 2‐4 days later the tumors had grown to their preregression size. In the growing and regressing tumor we have investigated: (1) the content of RNA, DNA and protein per g wet weight; (2) in vivo incorporation for 45 min of 32P‐orthophosphate into RNA and DNA and the 35S‐methionine incorporation into protein; (3) SDS polyacrylamide gel electrophoresis of soluble proteins after in vivo incorporation of 14C‐ and 3H‐leucine. The RNA content per g wet weight was found to decrease during regression and to increase during regrowth. DNA and protein content showed no variation. RNA/DNA ratio thus varied in parallel to the RNA content. The precursor incorporation into all three macromolecular species decreased during regression. The incorporation into DNA showed the most pronounced decrease. After readministration of hormones, regrowth was accompanied by a rapid increase in precursor incorporation into RNA, while the incorporation into DNA showed a lag of 1 to 2 days. SDS polyacrylamide gel electrophoresis was carried out with soluble proteins labelled in vivo with 14C‐ and 3H‐leucine during regression and regrowth, respectively. No differences in 14C/3H ratios could be demonstrated for the major fractions detectable in the electropherogram.
Establishment of EBNA‐expressing cell lines by infection of Epstein‐Barr virus (EBV)‐genome‐negative human lymphoma cells with different EBV strains
Authors: Fresen K. O. , Hausen H. Zur
Published: February 2007

Cells of two EBNA (Epstein‐Barr virus nuclear antigen)‐negative human lymphoma cell lines, BJAB and RAMOS, were infected with two strains of Epstein‐Barr virus (EBV). In two different experiments, B95‐8 virus‐infected BJAB cells revealed a gradually increasing number of EBNA‐positive cells. Twenty weeks after infection almost 100% of the cell population expressed this antigen. In contrast, it has not so far been possible to convert RAMOS cells into an EBNA‐positive cell line. The initial proportion of 35% EBNA‐positive cells declined to about 10% 20 weeks after infection. The development of EBNA‐positive multinuclear giant cells was a characteristic feature of infection with B95‐8 virus. EA (early antigen) and VCA (virus capsid antigen) appeared in less than 0.1% of the cell population after induction with IUdR only. Infection of BJAB and RAMOS cells with P3HR‐1 virus finally resulted in both cases in EBNA‐positive lines. In contrast to B95‐8 virus, the number of EBNA‐positive cells remained below 1% during the first 6 to 8 weeks. A sudden increase occurred thereafter, bringing the number of EBNA‐expressing cells to almost 100% within the following 4 weeks. During this period, BJAB but not RAMOS cells revealed a small number of EA‐ as well as VCA‐positive cells (<0.1%). Thus, reinfection by spontaneously released virus may explain the sudden increase in EBNA‐positive BJAB cells. Two distinct patterns of EBNA staining in P3HR‐1 virus‐infected cells were observed. They may suggest a genetic heterogeneity of this virus preparation.
Clonal transformation of human leukocytes by Epstein‐barr virus in soft agar
Authors: Yamamoto Naoki , Hinuma Yorio
Published: February 2007

The B95‐8 strain of Epstein‐Barr virus (EBV) induced colony formation of human umbilical cord‐blood leukocytes in soft agar medium. One‐hit response relationship between the number of colonies and the virus dose was observed with high dilutions of the virus preparation. However, there was a presumed cell‐killing effect with low dilutions of virus. The colonies were similarly induced, but with a lower efficiency, in adult peripheral blood leukocyte cultures infected with the virus. The colony‐forming activity of EBV was neutralized by anti‐EBV‐positive but not by negative human sera. The cells in colonies were capable of growing continuously and carried EBV‐associated nuclear antigen. Thus, it was evident that the colony formation was caused by clonal transformation by EBV.
Recent trends in breast‐cancer incidence and mortality in relation to changes in possible risk factors
Authors: Armstrong Bruce
Published: February 2007

Breast cancer incidence and mortality in England and Wales and the United States increased between 1950 and 1973, mainly in women aged between 45 and 64 years. These increases appeared to be partly cohort‐specific, beginning with cohorts born around 1899, and partly cross‐sectional, beginning in the mid‐1960s. In both countries, cohort‐specific decreases in fertility paralleled the cohort‐specific increases in breast cancer rates and may, at least in part, have been reponsible for them. Changes in other factors, such as age at menarche and menopause, use of rauwolfia derivatives and oestrogens, consumption of fat and meat, and breast cancer treatment were considered in relation to the cross‐sectional increases in breast cancer rates. On the evidence available, it was not certain that any of these could explain the breast cancer increases.
Lack of correlation between Marek's disease tumor induction and expression of endogenous avian RNA tumor virus genome
Authors: Calneck B. W. , Payne L. N.
Published: February 2007

Infection with Marek's disease virus (MDV) and subsequent tumor development failed to induce the expression of endogenous avian RNA tumor virus genome in Line‐151 and Line‐7 chickens which lacked such expression at 1 day of age. Titers of avian leukosis virus (ALV) group‐specific (gs) antigen detected by the COFAL test and expression of chick helper factor (chf) activity remained relatively constant in birds which expressed these genome functions at hatching time. Endogenous ALV belonging to the E‐subgroup was isolated from two of 50 birds; both were controls not exposed to MDV. There was no correlation between expression of ALV genome (gs or chf) at 1 day of age and the rate of tumor development subsequent to MDV infection. It was concluded that MDV infection can induce tumors without the participation of endogenous ALV genome.