bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices
Authors: Armstrong Bruce , Doll Richard
Published: February 2007

Incidence rates for 27 cancers in 23 countries and mortality rates for 14 cancers in 32 countries have been correlated with a wide range of dietary and other variables. Dietary variables were strongly correlated with several types of cancer, particularly meat consumption with cancer of the colon and fat consumption with cancers of the breast and corpus uteri. The data suggest a possible role for dietary factors in modifying the development of cancer at a number of other sites. The usefulness and limitations of the method are discussed.
The mechanism of carcinogenic action of 1,2‐dimethylhydrazine (sdmh) in rats
Authors: Pozharisski K. M. , Kapustin Yu. M. , Likhachev A. J. , Shaposhnikov J. D.
Published: February 2007

The radioactivity level in blood, bile, urine and contents of parts of the gastro‐intestinal tract in rats was studied after subcutaneous administration of 3H‐1,2‐dimethylhydrazine (3H‐SDMH) which induces colonic tumours. The alkylation of DNA, RNA and protein in the intestinal mucosa, liver and kidneys was estimated 1 h to 28 days after 3H‐SDMH treatment from the 3H‐incorporation into these macro‐molecules. Administration of 3H‐1,2‐diethylhydrazine (3H‐SDEH) which does not induce intestinal tumours was made as a control. Fifteen to 30 min after 3H‐SDMH treatment, marked radioactivity was found in blood, bile, urine and in contents of all regions of gastro‐intestinal tract. After 3H‐SDMH administration no label occurred in the contents of localized segments of gastro‐intestinal tract although it was present in blood, bile and urine. 3H‐SDMH methylated DNA, RNA and proteins of intestinal mucosa, liver and kidney to a high degree. One hour after 3H‐SDMH treatment the incorporation of label into protein of intestinal mucosa was higher than into liver and kidneys. 3H‐SDEH did not alkylate macromolecules in these organs but did so in thymus, spleen and brain, which are target organs for this carcinogen. After total hepatectomy. 3H‐SDMH did not methylate macromolecules of the intestinal mucosa. The following mechanism for the carcinogenic effect of SDMH is suggested. A carcinogenic metabolite of SDMH forms, in the liver, a conjugate with glucuronic acid. This glucuronide enters the gut both with bile and directly via the circulation. Microbial β‐glucuronidase releases the active metabolite which, in turn, alkylates tissue macro‐molecules.
Rat cell line 3y1 and its virogenic polyoma‐ and SV40‐transformed derivatives
Authors: Kimura Genki , Itagaki Asao , Summers Jesse
Published: February 2007

Cell lines were established from cultures derived from Fischer rat embryos according to the transfer schedule described by Todaro and Green (1963) for mouse 3T3 cells where cell crowding and serum exhaustion were kept to a minimum. Cell growth rate did not decline greatly during the course of successive 3‐day transfers. Like 3T3 cells, the rat cell lines possess very low saturation densities under standard culture conditions. A clonal cell line with a relatively high plating efficiency was obtained from one of the cell lines, 3Y1. In these cloned cultures, virus growth was not detectable upon infection with SV40, while a small amount of virus was produced upon infection with polyoma virus. Morphological transformation of the cloned 3Y1 cells by SV40 and polyoma virus could be assayed with single‐hit kinetics and with efficiencies comparable to those of the previously available transformation systems for each virus. Independent cell lines transformed by SV40 were consistently virus‐free and all the lines tested produced SV40 upon fusion with permissive monkey cells. Most of the independent transformed cell lines isolated after polyoma infection appeared to be virus‐free, although the cultures of some lines produced a small amount of polyoma virus spontaneously after a prolonged cultivation. Most of the virus‐free polyoma‐transformed lines produced virus upon fusion with permissive mouse cells.
Induction of specific changes in the surface membrane of myeloid leukemic cells by steroid hormones
Authors: Lotem Joseph , Sachs Leo
Published: February 2007

Normal mature macrophages and granulocytes have surface membrane receptors for specific immunoglobulin and immunoglobulin complement, which can be detected by rosette formation with erythrocytes coated with antibody (EA) or with antibody and complement (EAC). There are three types of myeloid leukemic cells, IR+D+, IR+D− and IR−D−. IR+D+ cells were induced to form receptors for EAC but not for EA by the steroid hormones prednisolone, dexamethasone and estradiol. Induction required protein synthesis and was not inhibited by cordycepin or vinblastine. Optimum induction required the continued presence of the hormones. IR+D+ cells were also induced by these hormones to migrate in agar, attach to the surface of a Petri dish and form macrophages. IR+D− cells showed a lower inducibility by these hormones and no formation of macrophages. There was no induction of any of these changes with IR−D− cells. The steroid hormones progesterone, testosterone and cortisone did not induce these changes in any of the leukemic cells and inhibited induction by prednisolone, dexamethasone and estradiol. The results indicate that specific surface membrane changes in myeloid leukemic cells can be induced by certain steroid hormones.
Oncogenic transformation of primary hamster cells by herpes simplex virus type 2 (HSV‐2) and an HSV‐2 temperature‐sensitive mutant
Authors: Kimura Susumu , Flannery Virginia L. , Levy Barnet , Schaffer Priscilla A.
Published: February 2007

Six oncogenically transformed cell lines were obtained following infection of hamster embryo fibroblasts with UV‐irradiated herpes simplex virus type 2 (HSV‐2) or with an HSV‐2 temperature‐sensitive mutant. All lines produced undifferentiated fibrosarcomas in newborn hamsters, four of the six lines produced metastatic tumors in the lung, and sera from tumor‐bearing hamsters contained neutralizing antibody to HSV‐2. HSV‐specific cell‐surface antigen (s) was detected by immunofluorescence tests in all six of the lines established from primary tumors. Antibody to an early, HSV‐specific, non‐structural polypeptide (VP134) reacted by immunofluorescence with antigen (s) in fixed preparation of three of the six tumor‐cell lines.
Specific anti‐tumor responses by cultured immune spleen cells. I. In vitro culture method and initial characterization of factors which block immune cell‐mediated cytotoxicity in vitro
Authors: Nelson Karen , Pollack Sylvia B. , Hellström Karl Erik
Published: February 2007

Spleen cells from BALB/c mice which either bore syngeneic sarcomas or were normal controls were cultured in vitro. The culture supernatants of spleen cells from tumor‐bearing mice inhibited (blocked) specific cell‐mediated cytotoxicity to the tumor borne by the spleen donor. They also mediated specific antiserum‐dependent cytotoxicity with control lymphoid cells. The appearance of blocking activity in culture supernatants was prevented by lysis of Q‐positive spleen cells with antiserum and complement. The blocking activity was removed by passing culture supernatants through an anti‐mouse immunoglobulin affinity column and was recovered in a 3 M NaSCN eluate of the column.
Human meningioma antigens
Authors: Winters W. D. , Rich J. R.
Published: February 2007

Sera from patients with various types of central nervous system tumors display antibodies reactive in serologic assays with cells and extracts derived from human brain neoplasms. Soluble antigens extracted and purified from surgical specimens of human meningiomas (MSA) were used to test for precipitating antibodies in sera from patients with various histologic types of brain tumors, non‐neural solid tumors and from normal donors. Blind studies by immunodiffusion (ID) showed that 63% (15/24) of meningioma patients, 53% (9/17) of glioma patients and 17% (5/29) of patients with various other brain neoplasms had antibodies that reacted with two of three meningioma‐associated antigens. Sera from normal donors and patients with non‐neural solid neoplasms reacted to a limited extent (7/118) with another of these tumor‐associated antigens. Cross‐reaction and absorption studies revealed that the three meningioma‐associated antigens were detecting different antibodies. None of the antigens was related to HLA antigens or to the human non‐neurotropic viruses used in our assays.
Antibody patterns to herpesviruses in kaposi's sarcoma: Serological association of european kaposi's sarcoma with cytomegalovirus
Authors: Giraldo G. , Beth E. , Kourilsky F. M. , Henle W. , Henle G. , Miké V. , Huraux J. M. , Andersen H. K. , Gharbi M. R. , Kyalwazi S. K. , Puissant A.
Published: February 2007

Sera from patients with Kaposi's sarcoma (KS) were examined for antibody titres to cytomegalovirus (CMV), Epstein‐Barr virus (EBV) and herpes simplex virus (HSV) types 1 and 2 by four techniques: indirect haemagglutination (IHA), complement fixation (CF), virus neutralization (NT) and indirect immunofluorescence (IF). The patients were classified, according to the stage of disease, as progressive and regressive. Control sera were obtained from healthy adults, matched for age, sex, race, socio‐economic status and geographic location, as well as from patients with melanoma, some of whom were receiving chemotherapy similar to that given to the KS patients. All KS sera contained CMV‐neutralizing antibodies. Seventy‐five percent of the European KS patients, mainly regressors, showed elevated anti‐CMV titres by IHA with a significant increase in the geometric mean over the corresponding healthy adult group and the melanoma group. An overrepresentation of high anti‐CMV titres, although less marked, was found by CF. There was no significant association with antibodies to EBV, HSV‐1 and HSV‐2 related antigens. By contrast, the African KS patients, mainly progressors, did not show a serologic association with CMV or with EBV and HSV‐1 and 2. The implication of these results is discussed.
Immunological studies of women with primary breast carcinoma
Authors: Jeejeebhoy H. F.
Published: February 2007

Lymphocytes from disease‐free women and women with primary breast carcinoma were comparable vis‐a‐vis their capacity to inactivate breast tumor cells in vitro. Sera from comparable numbers of women in each of these two groups either blocked, potentiated or left unaffected the anti‐tumor‐cell cytotoxicity of their lymphocytes. As such, the results cast doubt on the validity of the hypothesis that there is a positive correlation between the presence of humoral blocking factors and in vivo tumor progression.
Lectin agglutinability of non‐neoplastic and neoplastic human lymphoid cells in vitro
Authors: Glimelius Bengt , Nilsson Kenneth , Pontén Jan
Published: February 2007

Agglutination by two lectins, Concanavalin A (Con A) and Ricinus communis agglutinin (RCA), has been investigated in a human lymphoid cell system. The main conclusions of this study are: (1) no systematic correlation exists between the neoplastic state and sensitivity to Con A or RCA; (2) cells of neoplastic lines vary unsystematically in their surface properties as evaluated by Con A agglutination, with the possible exception that presence of Epstein‐Barr virus (EBV) is associated with a high degree of agglutination and (3) cells of diploid lymphoblastoid lines and phytohemagglutinin (PHA)‐stimulated lymphocytes agglutinate similarly and significantly better than unstimulated T‐ or B‐lymphocytes. The relatively simple Con A agglutination assay can be used as an adjunct in classification of human lymphoid cell lines.
Origin and partial characterization of Fc receptor‐bearing cells found within experimental carcinomas and sarcomas
Authors: Kerbel R. S. , Pross H. F. , Elliott E. V.
Published: February 2007

A variety of marine connective and epithelial tissue tumors, including the SAD/2 and FS9 fibrosarcomas, the TA3/Ha and CAD/2 mammary carcinomas and a primary methylcholanthrene‐induced sarcoma, were found to contain a high proportion of cells with receptors for the Fc portion of immunoglobulin G (“Fc receptors”). Experiments were undertaken to assess whether these cells were neoplastic, or whether they represented the infiltration into the tumor of non‐malignant host cells such as macro‐phages or lymphocytes. It was found that long‐term established in vitro cell lines of the TA3/Ha SAD/2 and CAD/2 tumors were entirely negative for the Fc receptor, whereas injection of these cells led to the formation of tumors containing a high proportion of Fc receptor‐bearing cells. Many of these cells were actively phagocytic as assessed by ingestion of iron filings or antibody‐coated erythrocytes. Injection of Fc receptor‐negative cultured tumor cells into F1 hybrids, in which host cells could be distinguished from the tumor cells by anti‐H2 sera, revealed that many or all of the Fc receptor‐bearing cells in the resultant tumor were of host origin. In contrast to its effect on normal spleen cells, anti‐θ serum treatment also partially inhibited Fc rosettes, suggesting a T‐lymphocyte origin for some of the Fc receptor‐bearing cells. Since almost all cells with potential anti‐tumor activity bear Fc receptors, it is suggested that an index of host cell infiltration of carcinomas and sarcomas can quickly and easily be ascertained by enumeration of Fc receptor‐bearing cells.
Lung cancer and smoking in Danish women
Authors: Jensen Ole M.
Published: February 2007

In most developed countries, including Denmark, cancer of the lung is the most frequent malignant disease among men, whereas the problem is less among women. Examination of Danish mortality data for the period 1931 to 1972 reveals a 5‐fold increase in female rates as opposed to a 16‐fold increase in male rates. Since about 1960 female rates have, however, increased faster than male rates with a consequent decline in the male‐female ratio. It is demonstrated that more recent female birth‐cohorts have higher mortality rates than the older ones. The increasing mortality from lung cancer among more recent female cohorts is shown to parallel increasing proportions of smokers in these cohorts. Further data are presented to indicate that not only is smoking more widespread among young than among old women, but the proportion of cigarette smokers among all smokers falls from 98% in the youngest to 33% in the oldest age‐group. No causal relationship between smoking and lung cancer can be claimed from the evidence presented. The present findings are, however, what would be expected if cigarette‐smoking were an aetiological factor in female lung cancer.
Inhibition of syngeneic fibrosarcoma growth by lymphocytes sensitized on tumor‐cell monolayers in the presence of the thymic humoral factor
Authors: Small Myra , Trainin Nathan
Published: February 2007

The present experiments were performed to investigate the possibility of inhibiting tumor growth in vivo with syngeneic lymphocytes sensitized in vitro on monolayers of the tumor under test, and to study the effect of a thymic humoral factor (THF) in this sensitization process. Monolayers of fibrosarcoma cells were used to sensitize spleen cells from syngeneic donors against the tumor. Such sensitized lymphocytes manifested cytotoxic activity against cells of the fibrosarcoma in a microassay measuring tumor‐cell detachment. However, when the sensitized lymphocytes were mixed with the fibrosarcoma cells and injected into syngeneic mice, enhanced tumor growth was observed in vivo. Addition of thymic humoral factor to the cultures during sensitization resulted in increased cytotoxic activity by the lymphocytes in vitro and a reduction in the tumor enhancement caused by these cells when injected in vivo. Enhanced tumor growth occurred when activated lymphocytes of allogeneic as well as syngeneic origin were injected together with the fibrosarcoma cells. Enhancement, which was already apparent when the spleen cells had been sensitized for 24h, could be circumvented by separate administration of lymphocytes and tumor cells. Syngeneic lymphocytes injected systemically after sensitization for 5 days exerted anti‐tumor reactivity against the fibrosarcoma grafted in the foot‐pad of syngeneic mice. Tumor growth was further inhibited by systemic injection of lymphocytes which had been sensitized in the presence of the thymic humoral factor.
Reactivity of serum from rous‐sarcoma‐bearing chickens with autochthonous and with allogeneic tumor cells: Preferential autochthonous recognition
Authors: Wainberg M. A. , Markson Y. , Doljanski F. , Weiss D. W.
Published: February 2007

Complement‐mediated cytotoxicity and indirect immunofluorescence assays showed that sera from random‐bred chickens bearing Rous sarcoma (RS) tumors are usually more reactive in vitro against RS cells of autochthonous than of allogeneic origin. Absorption of such sera with autochthonous, but not with allogeneic, RS cells abrogated the fluorescence staining capacity. Sera from tumor‐bearing birds did not stain normal chicken embryo cells (CEC), but reached with a higher proportion of CEC transformed by the RS virus than with cultured RS tumor cells. Tumor cells incubated at 37° C with autochthonous serum and fluorescent horse anti‐chicken immunoglobulin conjugate displayed cell surface fluorescence patching.
Temperature‐sensitive mutants of murine leukemia virus. V. Impaired leukemogenic activity in vivo
Authors: Greenberger Joel S. , Stephenson John R. , Aaronson Stuart A.
Published: February 2007

The in vivo biologic activities of a clonal isolate of the Rauscher strain of murine leukemia virus and several conditional lethal mutants with impaired replicative functions at the non‐permissive temperature were investigated. The parental virus induced a rapidly developing lymphoid leukemia in a high percentage of NIH Swiss mice inoculated as newborns. Mice inoculated in parallel with temperature‐sensitive mutant viruses showed no evidence of disease. The implications of these findings with regard to the requirements for type‐C virus replication to permit oncogenic transformation of lymphoid cells in vivo are discussed.
Soluble tumour‐specific antigen and its relationship to tumour growth
Authors: Thomson D. M. P.
Published: February 2007

Hooded rats bearing a syngeneic methylcholanthrene‐induced tumour were evaluated for extent of in vivo host immunity and this was correlated by in vitro techniques with the levels of circulating tumour antigen and specific antibody. Early tumour growth was associated with detectable immunity, as measured by the capacity of the animal to reject a second direct challenge of the same tumour at a remote site. Radio‐immunoassay for circulating tumour antigen and indirect membrane immunofluorescence for antitumour antibody did not detect either component at this stage. Animals with advanced tumours lost immunity as detected by direct tumour challenge, and this closely coincided with the appearance of rising levels of circulating soluble tumour antigen. Although the host possessed the immunologic ability to react against its own neoplasm, this ability was insufficient to produce tumour rejection. Active immunotherapy initiated at the time of, or up to 10 days after, intramuscular challenge with tumour, increased tumour immunity sufficiently for tumour growth to be prevented. Successful immunization was associated with the early appearance (16 days) of measurable levels of antitumour antibody and absence of circulating antigen. It is concluded that soluble tumour antigen present in the local microenvironment of the tumour in the early stages of tumour growth interferes with the ability of immune cells to cause tumour rejection. As the tumour progressively grows, sufficient soluble antigen is produced and released systemically to suppress the effector arm of the host's tumour immune response at distant sites. The levels of circulating soluble tumour antigen attained may be of critical importance in the suppression of rejection responses that prevent metastasis.
Ultraviolet inactivation of Epstein‐Barr virus: Effect on synthesis of virus‐associated antigens
Authors: Sairenji Takeshi , Hinuma Yorio
Published: February 2007

The relative sensitivity to ultraviolet (UV) light of genome functions of the P3HR‐1 strain of Epstein‐Barr virus (EBV) was studied. The formation of viral capsid antigen (VCA) appeared to be more sensitive than that of early antigen (EA), while the synthesis of membrane antigen (MA) was most resistant, as seen on examination in the presence of cytosine arabinoside (Ara‐C). However, the appearance of both VCA and EA, but not that of MA, was delayed with UV‐irradiated virus, in either the presence or absence of Ara‐C. The synthesis of EA and VCA induced by UV‐irradiated virus was suppressed in the presence of Ara‐C, while that of MA was not.
Nasopharyngeal carcinoma. X. Presence of Epstein‐Barr genomes in separated epithelial cells of tumours in patients from Singapore, Tunisia and Kenya
Authors: Desgranges C. , Wolf H. , De‐Thé G. , Shanmugaratnam K. , Cammoun N. , Ellouz R. , Klein G. , Lennert K. , Muñoz N. , Zur Hausen H.
Published: February 2007

Nasopharyngeal carcinoma (NPC) biopsies from Singapore, Tunisia and Kenya were compared, before and after separation of epithelial and lymphoid cells, for their EBV‐DNA content, using the cellular DNA‐EBV‐cRNA hybridization test. In all instances where successful separation of the two cell types was achieved, epithelial tumour cells showed a higher EBV‐DNA content than lymphoid cells or tumour before cell separation. It is, therefore, suggested that EBV‐DNA is mostly limited to epithelial cells. No significant difference was observed between NPC tumours originating from various geographical areas.
Characterization of the mononuclear cell infiltrate in human malignant melanoma
Authors: Roubin Régine , Césarini Jean‐Pierre , Fridman Wolf H. , Pavie‐Fischer Janine , Peter Hans H.
Published: February 2007

In the skin infiltrate of superficial spreading melanoma, non phagocytosing mononuclear cells (NPMC) represent a major cell component. The number of NPMCs decreases as a function of tumour progression. In addition, when an NPMC is in contact with a malignant melanocyte, the latter cell exhibits ultrastructural degenerative changes. In the blood of healthy donors and of melanoma patients, atypical mononuclear cells (AMC) can be identified. AMCs have been shown to participate in antibody‐dependent cellular cytotoxicity (ADCC) reactions against melanoma cells in vitro. In this paper, it is reported that NPMCs and AMCs have in common their size, and some ultrastructural features such as indented nuclei, dispersed organelles, rough endoplasmic reticulum profiles and surface microvilli. The two cell types are negative for non‐specific esterase. They also fail to react for peroxidase at either the light or the electron microscopic level. They do not adhere to glass. AMCs do not form spontaneous E rosettes, they have no surface IgG and they have no receptors for complement. However, they do form rosettes with EAIgG. On frozen sections firm binding of EAIgG has been seen on the skin infiltrate in three cases out of 10. It is concluded that NPMCs might react with tumour cells in vivo, in the same manner as do AMCs in vitro.
Tumour‐associated transplantation antigen in sera of rats with large RSV‐induced sarcomas
Authors: El Ridi Rashika , Bubeník H.
Published: February 2007

A factor inhibiting tumour growth in syngeneic hosts was found in the sera of inbred Lewis rats carrying Rous sarcoma virus‐induced tumour (RSL). The findings presented here suggest that the serum factor is a tumour‐associated transplantation antigen (TATA) shed from the neoplasm into the circulation. All the tumour‐bearers' sera tested with RSL cells were negative in indirect membrane immunofluorescence; however, on passive transfer into syngeneic rats, they protected the animals against the growth of an RSL tumour inoculum. A similar protective effect was also observed after injection of TATA prepared from RSL cell membranes by solubilization with potassium cholate. When incorporated into Freund's adjuvant, tumour‐bearers' sera immunized the animals against a subsequent RSL sarcoma graft. Sera collected from immunosuppressed rats bearing large sarcomas which presumably contain neither tumour‐specific antibody nor antigen‐antibody complexes, transferred inhibition of tumour growth to syngeneic hosts. Intact immunological reactivity of recipients was a necessary prerequisite for the protective effect of sera, since the passive transfer of an inhibitory serum to immunosuppressed rats did not inhibit tumour growth. We assume that the TATA present in tumour‐bearers' serum is released from the growing neoplasm as a result of either cell death or membrane metabolic turnover.
Intermittent chemotherapy and immunotherapy with BCG in remission maintenance of children with acute lymphocytic leukemia: Effects upon immunological function
Authors: Ekert H. , Jose D. G. , Wilson F. C. , Matthews R. N. , Lay H.
Published: February 2007

Twelve children with acute lymphocytic leukemia who had been in complete remission on continuous chemotherapy for at least 12 months, were treated with intermittent courses of chemotherapy alternating with BCG

BCG: Calmette‐Guérin strain of Mycobacterium bovis.

inoculation during the drug‐free intervals. Measurements were made of leukocyte populations in blood and bone marrow and of blastogenic responses of blood lymphoid cells to phytohemagglutinin and soluble leukemic blast cell membrane antigen. Antibody titers to a soluble leukemic blast‐cell membrane‐derived antigen were determined. Comparison was made with similar measurements during a second phase of intermittent chemotherapy without BCG inoculation (phase II). Two children showed bone‐marrow relapse and two developed central nervous system leukemia during the study. Rises in blood and bone‐marrow lymphoid cell numbers were found during both phases of the study. Blastogenic responses to phytohemagglutinin, depressed at the start of the study following at least 12 months of continuous chemotherapy, rose during intermittent chemotherapy and BCG and remained within normal ranges during phase II. Antibody titers and blastogenic responses to leukemia blast‐cell membrane antigens increased in eight of twelve and six of seven children respectively during the BCG phase and were maintained during phase II. Only one child showed further increases in phase II. The combination of BCG and intermittent chemotherapy may increase leukemia‐associated immunity in some patients with acute lymphocytic leukemia in remission. The separate contributions of either BCG or intermittent chemotherapy in producing this effect cannot be determined by this study.
Immunization against Marek's disease using Marek's disease virus‐specific antigens free from infectious virus
Authors: Lesnik F. , Ross L. J. N.
Published: February 2007

Immunity against Marek's disease was conferred by the use of non‐infectious materials extracted with non‐ionic detergents from cells infected with the attenuated strain of Marek's disease virus (MDV). Antibody‐free Rhode Island Red chicks were inoculated at 1 week of age with cell extracts emulsified in Freund's complete adjuvant and were given a second inoculation 1 week later without adjuvant. Protection against natural infection was obtained in groups inoculated with both soluble (not sedimented at 100,000xg/2 h) and insoluble antigens present in Nonidet P40 (NP40) extract, but only with the insoluble fraction of deoxycholate extract. The results suggest that the immunizing antigens can be partially solubilized with 0.5% NP40 and that the growth and spread of MDV are reduced in immunized chickens.
The relationship between nasopharyngeal carcinoma and the HL‐A system among tunisians
Authors: Betuel H. , Camoun M. , Colombani J. , Day N. E. , Ellouz R. , De‐Thé G.
Published: February 2007

Previous reports have demonstrated an association between the HL‐A system and risk for nasopharyngeal carcinoma among the Chinese in Singapore. The present paper describes an investigation of HL‐A profiles among NPC cases and non‐NPC controls from Tunisia, to determine whether a similar association occurs in a different ethnic group. A total of 109 NPC cases and 84 controls were typed. At the second HL‐A locus the results were similar to those found in Singapore, but the effect was less marked and did not reach high statistical significance. At the first HL‐A locus, no association between A2 and NPC was found, in contrast to the Singapore results.
Comparative in vitro sensitivity of two methylcholanthrene‐induced murine sarcoma lines to humoral and cellular immune cytotoxicity
Authors: Bataillon Georges , Pross Hugh , Klein George
Published: February 2007

MC57M and G are the tissue‐culture derivatives of two methylcholanthreneinduced murine C57Bl sarcomas. Their sensitivity to immune cytotoxic

In this report, the term “cytotoxicity”, unless otherwise qualified, will be used in the generic sense, covering such various in vitro effects of immune effectors as true cytotoxicity (actual reduction in the number of target cells), cytostasis (inhibition of target‐cell growth) and cytolysis. Clearly, other phenomena yet to be explored, such as cell adhesiveness or cell membrane permeability to isotopically‐labelled products, may well be involved in and interfere with the final outcome of some of the assays used in this work.

, cytostatic or cytolytic spleen cells and sera was compared in parallel in vitro assays. The level of cross‐reactivity displayed by the two lines was found to depend on the nature of the immune effector rather than on the assay which was used. It was high with immune spleen lymphocytes, alone or in the presence of decomplemented antisera, and low with antisera in the presence of rabbit complement. MC57G cells were more sensitive than MC57M cells to both effectors. Both cell lines were insensitive to antibody‐dependent cell‐mediated cytotoxicity. Preliminary evidence is presented, suggesting a probable involvement of embryonic and Moloney leukemia virus‐induced cell surface antigens in the in vitro sensitization of the two tumor lines to immune sera.
The response of Xeroderma pigmentosum cells and controls to the activated mycotoxins, aflatoxins and sterigmatocystin
Authors: Stich H. F. , Laishes B. A.
Published: February 2007

The activation of the mycotoxins aflatoxin B1, G1, B2, G2, aflatoxicol and sterigmatocystin by 9S fraction, microsomal preparation (105,000 × g) and supernatant (105,000 × g) of livers of several species was examined. DNA repair synthesis, chromosome aberrations and clone forming capacity were used as endpoints. Cultured fibroblasts of normal persons and DNA repair deficient Xeroderma pigmentosum patients were employed as test subjects. The activation mixtures significantly increase the chromosome breaking function, lethality and DNA damaging effect (measured as DNA repair synthesis) of aflatoxin B1, G1, aflatoxicol and sterigmatocystin. The DNA repair‐deficient XP cells respond to the activated mycotoxins with a low level of unscheduled 3HTdR incorporation as compared to that of control cells, but show a highly elevated sensitivity to the chromosome‐damaging and lethal effect of aflatoxin B1 and sterigmatocystin.
DNA repair synthesis of cultured human cells as a rapid bioassay for chemical carcinogens
Authors: San R. H. C. , Stich H. F.
Published: February 2007

The feasibility of detection of carcinogenic chemicals using DNA repair synthesis of cultured human fibroblasts as measured by an unscheduled 3HTdR incorporation has been explored. Of 64 chemicals tested, 29 were proximate or ultimate carcinogens, 15 were precarcinogens that required metabolic activation, 16 were non‐oncogenic compounds and 4 were of unknown carcinogenicity. All directly acting carcinogens triggered a DNA repair synthesis, whereas no unscheduled 3HTdR incorporation was observed following the application of the 16 non‐oncogenic compounds. As a rule, the precarcinogens (without metabolic activation) do not elicit DNA repair synthesis. However, longer exposures and higher concentrations of the precarcinogens 2‐AAF, aflatoxin B1 and sterigmatocystin gave unscheduled 3HTdR uptake. The results suggest the suitability of using repair synthesis as endpoint, and cultured human cells as subjects in a prescreening programme for chemical carcinogens.
Specific anti‐tumor responses by cultured immune spleen cells. II. Culture supernatants induce specific anti‐tumor cytotoxicity by non‐immune lymphoid cells in vitro
Authors: Nelson Karen , Pollack Sylvia B. , Hellström Karl Erik
Published: February 2007

Sera from tumor‐bearing mice induce specific cytotoxicity to tumor cells by non‐immune lymphoid cells (antiserum‐dependent cytotoxicity or ADC). When spleen cells from BALB/c mice bearing autochthonous or syngeneic sarcomas were cultured in vitro, culture supernatants were obtained which specifically sensitized sarcoma cells to injury in vitro by normal lymph‐node cells (LNC). Culture supernatants of spleen cells from mice whose transplanted sarcomas had been excised also induced ADC. The ADC activity resided in the mouse immunoglobulin fraction of the culture supernatants and its synthesis did not depend on the presence of theta‐positive cells. Following a brief in vivo exposure to culture supernatant with known ADC activity, LNC from non‐immune mice specifically destroyed tumor cells in an in vitro assay.
Appearance of C‐type virus‐like particles after co‐cultivation of a human tumor‐cell line with rat (XC) cells
Authors: Gabelman Norman , Waxman Samuel , Smith William , Douglas Steven D.
Published: February 2007

A serially propagated cell line (L104) was established by co‐cultivation of a lung adenocarcinoma (L‐1) from a patient with concurrent chronic lymphocytic leukemia and XC, a non‐producer rat line, known to carry the Rous sarcoma virus (RSV) genome. Karyotype of the L104 cultures revealed predominantly rat‐like patterns; however, about 5% of the cells reacted with HLA antibodies and demonstrated human isozyme patterns. Electron microscopy of L104 cells revealed the presence of C‐type particles budding from the cell membranes and in cytoplasmic vacuoles. Virus was not detected in any of the other normal lung, lung tumor or XC cells examined after co‐cultivation with XC cells. The particles isolated from tissue culture fluids had the biochemical and biophysical characteristics common to other known mammalian C‐type particles and were serologically related to the woolly monkey virus (WMV)/gibbon ape leukemia virus (GaLV) complex. Cross‐hybridization between viral 3H‐DNA transcripts and cellular RNAs from virus‐infected cells clearly show the presence of sequences in the L104 cellular RNA related to both the GaLV/WMV group of viruses and rat viruses. Hydroxyapatite chromatography reveals however that the primate‐related sequences in the viral RNA are indistinguishable from WMV in thermal elution profile. The host range of L104 virus appears to vary greatly from WMV in being xenotropic and, in the cell lines thus far tested appears, to infect only rat cells. The virus gave positive KC but negative XC assays. Inoculation of whole cells or cell‐free supernatants into weanling hamster did not result in either solid tumors or leukemia. Co‐cultivation of appropriate cell lines may represent an approach to the detection of latent viruses in human neoplasia.
Inhibition of in vitro lymphoproliferative responses to tumor‐associated antigens by suppressor cells from rats bearing progressively growing gross leukemia virus‐induced tumors
Authors: Glaser Moshe , Kirchner Holger , Herberman Ronald B.
Published: February 2007

W/Fu rats were injected subcutaneously with low numbers of cells from the Gross leukemia virus‐induced lymphoma, (C58NT) D, which induced transient tumor growth and regression (regressors), or with high numbers of tumor cells resulting in progressive tumor growth (progressors). Spleen cells from regressors had a significant reactivity in the mixed leukocyte tumor cell interaction (MLTI), while spleen cells from progressors were unresponsive. Similarly, the responses to the non‐specific mitogens, phytohemagglutinin and concanavalin A, were suppressed in spleen‐cell cultures of progressors. Passage of spleen cells from progressors over rayon adherence columns or pretreatment with an iron/magnet technique resulted in almost complete restoration of MLTI and mitogen responses. Addition of spleen cells from progressors depressed the MLTI of spleen cells from regressors and the mitogen reactivity of normal spleen cells. Serum from progressors also suppressed MLTI and mitogen reactivity. These data indicate that, in spleens of rats bearing progressively growing tumors, suppressor cells can be demonstrated which inhibit specific reactivity to tumor‐associated antigens and non‐specific reactivity to mitogens. The presence of suppressor cells or of inhibitory factors in the serum may contribute to the immunosuppression frequently observed in tumor‐bearing hosts.
Genetic control of oncogenesis by murine sarcoma virus moloney pseudotype. I. Genetics of resistance in AKR mice
Authors: Colombatti A. , Collavo D. , Biasi G. , Chieco‐Bianchi L.
Published: February 2007

Injection of Moloney mouse sarcoma virus (M‐MSV) in adult mice of several inbred strains revealed that all strains except AKR are highly susceptible to M‐MSV tumor development. F1 hybrids between AKR and CBA, DBA/2 or NIH mice are as resistant (93%) as the parental AKR strain, which indicates that resistance is transmitted as a dominant character. First backcross mice to the susceptible parent show a 3:1 ratio of resistant to susceptible mice. This is the expected ratio for two segregating loci which independently confer resistance. The incidence of resistant F2 mice is somewhat lower than expected. Further support for the two‐gene hypothesis was obtained in second backcross mice. None of the major genes affecting MuLV infection (Fv‐2 and H‐2) seems to play any role in this system and no linkage was found with Thy. 1 and albino, dilute, agouti and brown markers.
Genetic control of oncogenesis by murine sarcoma virus moloney pseudotype. II. A dominant epistatic susceptibility gene
Authors: Colombatti A. , Collavo D. , Biasi G. , Chieco‐Bianchi L.
Published: February 2007

We have shown in the preceding paper that AKR mice are highly resistant to M‐MSV tumor development, and that resistance is transmitted as a dominant character In the present studies the tumor‐response pattern of F1 hybrids between resistant AKR and susceptible strains (C57Bl/6, BALB/c and BIOBR) following injection with Moloney mouse sarcoma virus (M‐MSV) resembles that of the non‐AKR parent. Segregation is observed in first backcross (Bcl) and F2 mice, and the segregation ratios up to Bc3 mice fit a one‐gene model. The data of triple cross hybrids suggests that this dominant susceptibility gene inhibits the phenotypic expression of M‐MSV tumor resistance in some susceptible Fv‐1bb strains as well as in their hybrids with AKR. Neither Fv‐1 nor H‐2 exerts any significant influence on this complex system.
Studies of lymphocyte stimulation by intact tumor‐cell and solubilized tumor antigen
Authors: Dean J. H. , McCoy J. L. , Lewis D. , Appella E. , Law L. W.
Published: February 2007

BALB/c mice were rendered immune to a syngeneic SV40‐induced sarcoma by subcutaneous injection of mKSA‐TU5 tissue‐culture adapted cells. Spleen cells from immune mice were examined for tumor‐cell neutralization in the Winn assay as well as in in vitro lymphocyte stimulation assays. A microculture (200 μl) lymphocyte stimulation (LS) assay utilizing immune spleen cells was employed with mixed lymphocyte/tumor‐cell cultures (MLTC) and with papain crude soluble (CS) extracts from mKSA‐TU5 cells. Specificity in the LS assay was determined using spleen cells from mice immune to other syngeneic tumors and by soluble antigenic preparation of normal BALB/c spleen cells. The Winn assay studies demonstrated that spleen cells from mKSA‐sensitized mice neutralized mKSA tumor cells and this was corroborated by their resistance to direct tumor challenge. Positive lymphocyte transformation responses in MLTC were observed when mKSA‐TU5‐sensitized spleen cells were mixed with mitomycin‐C‐treated intact tumor cells or when papain‐solubilized antigens of mKSA cells were employed, but not with non‐immune spleen cells or with a soluble antigen from normal cells. Papain‐solubilized antigen preparations employed in in vitro assays also immunized against challenge with mKSA tumor cells. Specificity of these lymphocyte transformation reactions was demonstrated with non‐sensitized lymphoid cells or lymphoid cells from mice sensitized with a syngeneic Kirsten virus‐induced sarcoma (KA‐31) or a mineral‐oil‐induced plasmacytoma (Adj‐PC5), which failed to respond. Thus, mKSA tumor surface antigens were recognized on intact tumor cells or with microgram quantities of papain‐solubilized extracts from these tumor cells. We believe the lymphocyte stimulation assay affords a method for demonstrating the presence of tumor‐specific antigen and for monitoring further purification procedures.
Detection of virus‐specific DNA sequences by quantitative in situ hybridization during infection with SV40
Authors: Langelier Yves , Mandeville Rosemonde , Simard René
Published: February 2007

In situ hybridization has been used as a quantitative method to study the replication of SV40 during lytic infection. Various parameters have been defined such as fixation and denaturation of cytological preparations, concentration of complementary (3H)‐cRNA and volume of buffer used for the hybridization reaction. When all these parameters are carefully controlled, a reproducibility of ±10% can be obtained for the quantitative study of the system SV40‐monkey kidney cells (CV‐1). In this system, it is evident that the synthesis of viral DNA is not localized in a special area of the nucleus and that it is not synchronized in confluent cells. Moreover, a proportion of 20 to 30% of cells are not labelled whatever the multiplicity of infection. In SV40‐transformed cells, it was not possible to detect significantly the integrated genome due either to the small size of the genome or to the fact that the number of genome‐equivalents integrated at the same place is too low to yield a radioactivity superior to background level for long periods of exposure.
Specific anti‐tumor responses of cultured immune spleen cells III. Further characterization of cells which synthesize factors with blocking and antiserum‐dependent cellular cytotoxic (ADC) activities
Authors: Nelson Karen , Pollack Sylvia B. , Hellström Karl Erik
Published: February 2007

Spleen cells from BALB/c mice bearing syngeneic, methylcholanthrene‐induced sarcomas were cultured in vitro. In agreement with previous observations, two tumor‐specific activities could be demonstrated in the culture supernatants: the supernatants suppressed (blocked) specific lymph‐node cell‐mediated cytotoxicity directed against the respective neoplasm and they induced specific antibody‐dependent cellular cytotoxicity (ADC) mediated by lymph‐node cells from non‐immune mice. In the present study, the effects of specific depletion or enrichment of different cell types on the ability to synthesize the blocking and ADC activities was explored. Spleen cells passed through columns of Sephadex G‐10, which removed plasma cells and macrophages, no longer synthesized factors with ADC activity though synthesis of blocking factors continued. However, lysis of Thy‐1‐positive cells with antiserum and complement did abolish the synthesis of blocking factors. Spleen cells from tumor‐bearing mice were then enriched for Thy‐1‐positive cells by selective removal of macrophages and plasma cells on G‐10 columns and of immunoglobulin‐bearing cells on anti‐mouse immunoglobulin affinity columns. This T‐cell‐enriched population synthesized blocking factors and restored blocking factor synthesis in cultures depleted of Thy‐1‐positive cells. Similarly enriched spleen cells from normal control mice did not synthesize tumor‐specific blocking factors but partially restored synthesis of blocking factor in tumor‐bearer spleen cultures depleted of Thy‐1‐positive cells.
Production of epithelial and mesenchymal tumours with rat liver cells transformed in vitro
Authors: Montesano R. , Vincent L. Saint , Drevon C. , Tomatis L.
Published: February 2007

Epithelial‐like cells originating from the livers of 10‐day and 8‐week‐old BD rats were established in culture. The cells were treated in vitro for 1 or 4 weeks with dimethyl‐nitrosamine (DMN) or N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG). Although some structural changes were observed in treated cells, it was not possible to score for morphological transformation in vitro. Newborn syngeneic rats were injected with 1.5‐2 × 106 treated or 1.5‐5 × 106 control cells at various times up to 38 weeks from the beginning of treatment with the carcinogen. Following the injection of DMN‐treated cells, a total of 32 of the 42 injected rats developed tumours, of which 17 were epithelial, 10 carcinosarcomas and 5 fibrosarcomas. Following the injection of the MNNG‐treated cells into 61 rats, a total of 30 tumours were observed, including 8 carcinomas, 9 carcinosarcomas and 13 fibroscarcomas. Tumours, mainly of the mesenchymal type, were also observed in rats inoculated with control cells but at a lower frequency. The observation of mesenchymal tumours is attributed to the presence of a mixed population of epithelial and mesenchymal cells in the original culture.
Human endometrial carcinomas serially transplanted in nude mice and established in continuous cell lines
Authors: Merenda C. , Sordat B. , Mach J. P. , Carrel S.
Published: February 2007

Three out of five human endometrial carcinomas were successfully grafted into nude mice (BALB/c/nu/nu). Two of these tumors could be maintained by serial transplantation. The morphological characteristics displayed by the grafted tumors were comparable to those of the original carcinomas. Permanent cell lines were established from these two tumors. Reinjection of cells grown in vitro into nude mice produced nodules of identical histology as compared to original solid transplants. The influence of medroxy‐progesterone acetate on tumor growth in vivo and cell proliferation in vitro was studied. This hormonal treatment did not produce any significant effect on tumor cells, either in vitro or in vivo, for the two endometrial carcinomas. After medroxyprogesterone administration, a slight but non‐significant growth inhibition of the tumor cells in vitro was observed and the tumor transplants in vivo did not appear to be influenced. The experiments illustrate the possible use of this model for testing potential anti‐cancer agents.
Sequential in vitro reactivity of lymphocytes from melanoma patients receiving immunotherapy compared with the reactivity of lymphocytes from healthy donors
Authors: Berkelhammer Jane , Mastrangelo Michael J. , Laucius J. Frederick , Bodurtha Audley J. , Prehn Richmond T.
Published: February 2007

A microcytotoxicity technique was used to determine the sequential in vitro reactivity against melanoma cells of lymphocytes from melanoma patients receiving immunotherapy and from healthy donors. Lymphocytes were collected every 2 weeks for 2‐3 months and were stored in liquid nitrogen until use. Preliminary studies had indicated that freezing did not affect the reactivity of lymphocytes. Lymphocytes from 10 healthy donors tested against melanoma cells exhibited substantial reactivity which showed no consistent pattern over time. Lymphocytes from 9 melanoma patients exhibited increased reactivity after immunotherapy. Patterns of reactivity against melanoma cells and against bladder carcinoma cells were similar, indicating lack of specificity for melanoma antigens. Correlations with clinical course of the disease were not apparent.