bluuebunny/crossref_metadata_2025 huggingface dataset:
Large interindividual variations in metabolism of benzo(α)pyrene by peripheral lung tissue from lung cancer patients
Authors: Cohen Gerald M. , Mehta Rekha , Meredith‐Brown M.
Published: February 2007

A very large variation (44‐fold) was observed in the ability of short‐term organ cultures of peripheral lung tissue from lung‐cancer patients to metabolize the environmental carcinogen benzo(a)pyrene to organic solvent‐soluble metabolites. The amounts of benzo(a)pyrene (2 μM) metabolized ranged from little (1%) to almost total (96.2%) metabolism within 24 h of culture. Previous work by Kellerman et al. (1973) has suggested a relationship between susceptibility to lung cancer and the inducibility of aryl hydrocarbon hydroxylase activity in cultured human lymphocytes. The metabolic fate of carcinogenic polycyclic aromatic hydrocarbons in the respiratory tract in vivo is undoubtedly more closely mimicked by short‐term organ culture of human lung than by cultured lymphocytes. Thus the very wide interindividual variation observed in pulmonary metabolism of benzo(a)pyrene in this study and the large variations in covalent binding to human bronchial DNA observed by Harris et al. (1976) strongly suggest that there may be little basis for screening humans for variations in lymphocyte aryl hydrocarbon hydroxylase activity as a means of assessing their susceptibility to lung cancer.
Cytotoxicity against the K562 erythroleukemia cell line by human natural killer (NK) cells which do not bear free Fc receptors for IgG
Authors: Kay H. David , Fagnani Roberto , Bonnard Guy D.
Published: February 2007

When Fc receptors (FcR) on normal human peripheral blood lymphocytes were induced to modulate by overnight (18 h) incubation in the presence of soluble or particulate immune complexes, the natural killer (NK) activity of the effector lymphocyte suspension, as measured against the K562 erythroleukemia cell line, was significantly, but only partially, inhibited. The NK activity which remained was always strong, and was not significantly inhibited by inclusion of antigen‐antibody complexes in the cytotoxicity assay, nor was it further depleted by adsorbing the modulated cells on plastic surfaces coated with immobilized antigen‐antibody complexes. Antibody‐dependent cell‐mediated cytotoxicity (ADCC) against rabbit antibody‐sensitized Chang liver cells was totally abrogated following the modulation process, and could not be restored by exposure of modulated effector cells to trypsin, indicating that the FcR had actually been shed and were not merely being blocked with immune complexes. Although freshly isolated peripheral blood lymphocytes active in natural (or “spontaneous”) cytotoxicity have been shown to bear FcR, our data indicate that NK activity against the K562 cell line can be effectively mediated by NK cells which have lost their FcR. This supports the concept that NK activity against K562 is independent of FcR, and, therefore, of IgG.
Cytolytic activity of macrophages isolated from primary murine sarcoma virus (MSV)‐induced tumors
Authors: Taniyama Tadayoshi , Holden Howard T.
Published: February 2007

Macrophages isolated from regressing or progressing tumors induced by murine sarcoma virus (MSV) were tested for cytolytic activity in an 18‐h 51Cr release assay. Macrophages from the tumors of mice injected 14 days earlier with stocks of MSV‐producing regressor or progressor tumors had comparable levels of cytotoxicity. However, macrophages from the progressively growing tumors, 50–65 days after the inoculation with the progressor virus, had lower levels of cytotoxicity than those from the regressing tumors (day 14). On the other hand, macrophages from progressively growing MSV tumors (day 14) in nude mice had little or no detectable cytolytic activity. In a fractionation study, using the 1‐g velocity sedimentation technique, cells from regressing tumors (day 14) showed at least two peaks of cytolytic activity, one at about 4 mm/h and another at 6–7 mm/h, while cells from the progressing tumors (day 60) had only one peak of cytolytic activity, at about 4 mm/h. In contrast, none of the cell fractions of tumors from nude mice (day 14) showed cytolytic activity. Since bacterial lipopolysaccharide (LPS) has been shown to augment the cytolytic activity of primed macrophages, its effect on cells from MSV tumors was evaluated. Cytolytic activity of the cells from regressing or progressing tumors that had pre‐existing cytolytic activity was augmented by the addition of LPS during the assay period, but LPS treatment did not activate inactive fractions or change the distribution patterns of the cytolytic activity in fractions from 1‐g velocity sedimentation.
Analysis of the expression of H‐2 and H‐2‐linked antigens on mammary tumor cells
Authors: Snoek Margriet , Démant Peter
Published: February 2007

The products of the recently discovered H‐2L locus were expressed on BALB/c mammary tumor cells and behaved as histocompatibility antigens, in contrast to the products of H‐2 linked loci (Qa‐loci) that did not influence the acceptance or rejection of tumor transplants.
Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti‐interferon serum. VI. Polyoma virus infection
Authors: Gresser Ion , Maury Chantal , Kress Chantal , Blangy Daniel , Maunoury Marie‐Thérèse
Published: February 2007

We have determined the effect of a single injection of potent sheep anti‐mouse interferon globulin on polyoma‐virus‐induced early runting disease and tumor formation in Swiss mice. When newborn mice were injected with ≥9 × 106 PFU of polyoma virus, 16% (7/44) of mice runted and died in contrast to 96% (45/47) of mice injected with virus and anti‐interferon globulin. Likewise, a greater percentage of mice injected with lower doses of virus and anti‐interferon globulin developed tumors than did control virus‐injected mice. These results suggest that interferon is an important factor in determining the susceptibility of newborn mice to polyoma virus.
Loss of alpha‐fetoprotein in rat hepatoma culture cells
Authors: Yoo Tai‐June , Kuo Chao Ying , Patil Shivanand R. , Kim Untae , Cancilla Pasquale , Ackerman Larry D.
Published: February 2007

The production of alpha‐fetoprotein (AFP) by cultured rat Morris hepatoma 7777 hepatoma cells was studied. Initially, in vitro, rat hepatoma tumor cells synthesized and released AFP into the culture medium. As subculturing progressed, however, their ability to produce AFP diminished. After 8 months of in vitro cultivation, a non‐AFP‐producing tumor cell line had not lost its tumorigenicity and produced a solid tumor when injected into two groups of Buffalo rats. New tumors derived from tissue culture cells have shown significantly lower levels of serum AFP than the in vivo tumor line. However, another subline of this hepatoma tissue culture (7777 Iowa) did not lose its ability to produce AFP after 1 year of in vitro culture. Electron microscopy demonstrated no morphological change when the two different lines (AFP‐producing and non‐AFP‐producing) were compared. Chromosomal analysis in these cell lines revealed that the non‐AFP‐producing line (7777 TC) had 42% cells with a diploid or near‐diploid complement whereas the AFP‐producing (7777 Iowa) line showed a greatly variable aneuploidy number with 45% of the cells near tetraploidy. The reason for the virtual loss of AFP production or the different response of this tumor cell in the rat hepatoma culture remains unknown. Our studies and others indicate that, though AFP is an oncofetal antigen and a gene product of tumor cells, the control mechanism of AFP production could be an epiphenomenon of tumor cell and not related to the control of tumor growth and differentiation.
Cell surface sialylation of glycoproteins and glycosphingolipids in cultured metastatic variant rna‐virus transformed non‐producer BALB/c 3T3 cell lines
Authors: Yogeeswaran Ganesa , Sebastian Henry , Stein Barry S.
Published: February 2007

The sialic acid composition and the display of cell surface sialyl components of several metastatic variant RNA‐virus‐transformed non‐producer BALB/c 3T3 have been studied in culture. The following observations have been made concerning the sialyl components in these lines: (1) the compositions of whole‐cell total, protein‐bound and lipid‐bound sialic acid were not appreciably different; (2) the surface sialic acid studied using the neuraminidase‐galactose oxidase method and metabolic labelling followed by neuraminidase hydrolysis showed a positive correlation with the metastatic properties of these lines; (3) the degree of surface sialylation determined by galactose oxidase—sodium borotritide labelling of neuraminidasetreated and untreated cells revealed that 44–89% of exposed galactose and/or N‐acetyl galactosamine residues of total cell‐surface saccharides were sialylated in highly and intermediately metastatic lines as compared with 11–30% in the poorly and non‐metastatic lines; (4) the cell surface glycoproteins and glycosphingolipids contributed equally well in their degree of sialylation and there was a positive correlation with the metastatic properties of the cells in vivo; (5) the cell surface proteins labelled by the lactoperoxidase‐catalyzed iodination technique, followed by gel electrophoresis, showed some minor differences between metastatic variant lines. However, glycoproteins detected by the galactose oxidase labelling of neuraminidase‐treated and untreated cells showed major differences in composition between the metastatic variant lines. The study of four highly metastatic lines has shown that the cells of these lines were enriched in several sialyl‐glycoproteins, whereas three non‐tumorigenic lines and two poorly metastatic or non‐metastatic lines contained unsialylated glycoproteins. The results indicate an enhancement of the degree of sialylation of surface glycoconjugates accompanying the metastatic process in RNA‐virus‐transformed mouse lines.
Characterization of a type‐C virus produced by co‐cultures of human leukemic bone‐marrow and fetal canine thymus cells
Authors: Smith R. Guy , Nooter Kees , Bentvelzen Peter , Robert‐Guroff M. , Harewood K. , Reitz M. S. , Lee Sin Ai , Gallo R. C.
Published: February 2007

The putative human helper virus SKA‐21/A204V, isolated by Nooter et aal. in 1977 from human leukemic bone‐marrow cells following co‐culture with normal fetal canine thymus cells, Cf2th, has been characterized with respect to its major viral core protein, reverse transcriptase, and nucleic acid sequences. The results of these analyses show that this virus is not distinguishable from the woolly monkey type‐C virus, SSAV‐1, by the techniques employed.
Augmentation of cell‐mediated cytotoxicity to a rat lymphoma. I. Stimulation of non‐T‐cell cytotoxicity in vivo by tumour cells
Authors: Dawkins H. J. S. , Shellam G. R.
Published: February 2007

The injection of a syngeneic Gross‐virus‐induced lymphoma into W/Fu rats induced peaks of cytotoxicity in the spleen attributable to non‐T cells and T cells 3 and 10 days later, respectively. The conditions required for augmenting the cytotoxicity of the non‐T cells in various lymphoid compartments (shown elsewhere to closely resemble NK cells) were analysed using the ip and iv routes of inoculation and a variety of tumour cells including those normally susceptible or resistant to lysis by NK cells in vitro. Using an ip inoculation of W/FuG‐1 cells (a tumour susceptible to lysis by NK cells), a short‐lived, 3‐fold increase in cytotoxicity was observed in the spleen at day 3 and a 5‐fold increase in the PEC at day 5. Cytotoxicity in other lymphoid organs remained unchanged. Tumours resistant to lysis by NK cells also stimulated cytotoxicity in the spleen or PEC, although the effect depended on the dose and route of inoculation used, and depression of cytotoxicity was observed under some conditions.
Augmentation of cell‐mediated cytotoxicity to a rat lymphoma. II. Characterization of the non‐T cytotoxic cells stimulated in vivo by tumour cells as natural killer cells
Authors: Dawkins H. J. S. , Shellam G. R.
Published: February 2007

A variety of tumours injected into rats were found to rapidly stimulate cytotoxicity which was similar to naturally‐occurring cytotoxicity of normal rats. Cytotoxic cells from the spleen and peritoneal cavity closely resembled NK cells in their lytic specificity and cell‐surface characteristics. Thus, although cytotoxicity could be stimulated “non‐specifically” with tumours which were resistant to lysis in vitro by NK cells, the cytotoxic cells exhibited patterns of specificity against a panel of target cells in direct lysis or competitive inhibition assays which were similar to those of NK cells from normal rats. These cells also closely resembled NK cells in being largely non‐adherent, non‐T cells, and in exhibiting a similar heterogeneity in the expression of Fc receptors. Thus, cytotoxicity which was augmented shortly after tumour inoculation appeared to be attributable to NK cells. However, whilst the majority of NK cells from normal or tumour‐inoculated rats shared these properties, significant heterogeneity was observed Minor populations of cytotoxic cells were adherent, were lysed by a heterologous anti‐T‐cell antiserum and complement and did not express an Fc receptor, although it was not determined whether the same subpopulation possessed all three characteristics.
Tumor metastases and cell‐mediated immunity in a model system in DBA/2 mice. VI. Similar specificity patterns of protective anti‐tumor immunity in vivo and of cytolytic T cells in vitro
Authors: Bosslet K. , Schirrmacher V. , Shantz G.
Published: February 2007

In an attempt to analyze mechanisms of immunity against tumor metastases, protective anti‐tumor immunity in vivo was compared with cytotoxic T‐cell activity in vitro in a well‐defined syngeneic tumor model system. The system consists of a chemically induced parental tumor cell line (Eb) with little or no metastatic potential and a spontaneous variant thereof (ESb) with pronounced metastatic properties. Tumor protection experiments revealed the presence of tumor‐associated transplantation antigens (TATAs) on both Eb and ESb tumor cells. TATAs of Eb and ESb were found to be distinct and non‐cross‐reactive. One of several unrelated tumors, however, RL♂1, expressed TATAs which cross‐reacted with those of Eb. Protective immunity against the non‐metastasizing tumor was much stronger than that against the metastasizing variant. Furthermore, the optimal procedures for induction of immunity in vivo were strikingly different for each tumor. Tumor‐specific cytotoxic T lymphocytes (CTLs) were obtained after sensitization in vivo with viable tumor cells and restimulation in vitro for 4–5 days with mitomycin‐C‐treated autologous tumor cells. Both anti‐Eb and anti‐ESb CTLs showed high cytolytic activity in a 4‐h 51Cr release assay against the autologous tumor lines. The target antigens recognized by these cells were similar to the TATAs as defined in the protection experiments. (1) The target antigens of Eb and ESb were distinct and non‐cross‐reactive. (2) Only one of 14 unrelated syngeneic and allogeneic tumors expressed a target antigen which cross‐reacted with that of Eb. (3) This tumor was the radiation‐induced BALB/c lymphoma RL♂1 which also cross‐reacted at the level of the TATAs. The correlations between protective immunity obtained in vivo and cytolytic T cells induced in vitro suggest that cytolytic T cells can recognize TATAs and may thus play an important role in the establishment of protective immunity.
Effect of sodium butyrate on the antiviral and anticellular action of interferon in normal and MSV‐transformed cells
Authors: Bourgeade M. F. , Chany C.
Published: February 2007

Sodium butyrate enhances the antiviral and anti‐cellular action of interferon in MSV‐transformed cells but has no such effect in normal cells. The increased sensitivity could be mediated at least partially by the butyrate‐induced elaboration of the microtubule and microfilament network.
Molecular heterogeneity of alpha‐fetoprotein secreted by primary and transplantable hepatocellular carcinomas
Authors: Kelleher Philip C. , Smith Carol J.
Published: February 2007

Due to differences in carbohydrate content, rat AFP exhibits concanavalin A (Con A)‐binding heterogeneity. In order to investigate the control of the glycosylation of AFP synthesized by malignant cells, the patterns of AFP Con A affinity molecular variants secreted by sixteen 3′‐methyl‐4‐dimethyl‐aminoazobenzene‐induced primary hepatocellular carcinomas were followed sequentially during growth of the primary tumors through establishment as transplantable hepatocellular carcinomas. Fourteen of the transplantable tumors showed stable patterns of serum AFP Con A affinity molecular variants. Five of these 14 tumors secreted patterns of AFP Con A affinity molecular variants similar to the patterns found in the sera of the rats bearing the primary tumor of origin; the remainder of the tumors secreted an AFP Con A affinity molecular variant pattern which bore no relationship to that of the primary hepatocellular carcinoma of origin. Two of the transplantable hepatocellular carcinomas did not secrete stable proportions of AFP Con A affinity molecular variants during the 2‐year study. In 14 transplantable hepatoma lines the patterns of AFP Con A affinity molecular variants throughout successive transplant generations were significantly different from the pattern found in newborn rat serum. The stability of AFP Con A affinity molecular variant secretion by transplantable hepatocellular carcinomas indicates that the control of glycosylation of AFP and perhaps of other proteins is a heritable phenotypic property of these tumors and is consistent with other observations that the metabolic activities of transplantable hepatocellular carcinomas are constant over a period of years.
The differentiation of clonal rat yolk SAC tumor cell lines cultivated with dibutyryl‐cyclic 3′, 5′‐adenosine monophosphate
Authors: Tsukada Yutaka , Hibi Nozomu , Sakashita Shigeo , Abe Kazuhiro , Hirai Hidematsu
Published: February 2007

Five rat yolk sac tumor cell lines were cloned from a yolk sac tumor line which originally arose following fetectomy. The doubling time of each of the cloned tumor lines was about 50 h. All of the cloned tumor cell lines synthesized and secreted AFP and albumin but there was a gradual decrease in the synthesis of these proteins during serial passage. The cells formed clusters which looked like vitelline ducts or the parietal yolk sac and they also had basement membranes which closely resembled Reichert's membrane. When the cloned cell lines were cultivated in the presence of 1 mM dibutyryl cyclic‐AMP, myotube‐like and neuron‐like cells appeared. Acetylcholine esterase and creatine phosphokinase activity were present when myotube‐like cells were present whereas acetylcholine esterase activity predominated when neuron‐like cells were present.
Tritiated thymidine as a broad spectrum initiator in transplacental two‐stage carcinogenesis, with phorbol as promoter
Authors: Armuth Vlasta , Berenblum Isaac
Published: February 2007

A single subcutaneous injection of 200 μCi [3H] thymidine into pregnant BALB/c mice, followed by intraperitoneal injections of phorbol, twice weekly for 25 weeks, in the offspring, resulted in higher tumour development in the lungs and livers of male and, to a lesser extent, of female offspring, than in their untreated littermates. The difference in over‐all tumour incidence was statistically significant, but the increases of the individual tumour types were only of borderline significance. Slight carcinogenic activity of [3H]thymidine alone was observed in the mothers, and in the offspring, without phorbol treatment. The results suggest the possibility of using [3H]thymidine as a broad spectrum initiator for transplacental two‐stage carcinogenicity studies to determine the organ specificity of different promoting agents.
Occurrence of heat‐labile regan type of alkaline phosphatase in hematopoietic tumors
Authors: Damle S. R. , Shetty P. A. , Jussawalla D. J. , Bhide S. V. , Baxi A. J.
Published: February 2007

The physicochemical and immunological properties of alkaline phosphatase extracted from Hodgkin's nodes, non‐Hodgkin's lymphoma nodes and leukemic leukocytes have been studied. The alkaline phosphatase from these three tumor types possesses the same biophysical and biochemical properties and immunological determinants as the placental alkaline phosphatase. However, it is more heat‐labile than the placental isoenzyme. Immunological experiments indicate that, of these tumor types, Hodgkin's tumor contains the largest amounts of heat‐labile Regan type of alkaline phosphatase.
The initiation of tumours on mouse skin by dihydrodiols derived from 7,12‐dimethylbenz(a)anthracene and 3‐methylcholanthrene
Authors: Chouroulinkov I. , Gentil A. , Tierney B. , Grover P. L. , Sims P.
Published: February 2007

The cis‐2a,3‐diol and the trans‐4,5‐, trans‐7,8‐, trans‐9,10‐ and trans‐11,12‐dihydrodiols of 3‐methylcholanthrene and the trans‐3,4, trans‐5,6‐, trans‐8,9‐ and trans‐10,11‐ dihydrodiols of 7,12‐dimethylbenz[a]‐anthrancene have been tested, in comparison with the parent hydrocarbons, for their abilities to initiate skin tumours in female CDI mice. Groups of mice received a single topical application (25 μg) of a diol or of a hydrocarbon, and 1 week later repeated topical applications (1 μg) of 12–0‐tetradecanoyl‐phorbol‐13‐acetate were commenced. The results show that the diols capable of being converted into bay‐region vicinal diol‐epoxides, i.e. the 9,10‐diol of 3‐methylcholanthrene and the 3,4‐diol of 7,12‐dimethylbenz[a]anthrancene were active as initiating agents but that they were no more active than their parent hydrocarbon. The K‐region 5,6‐diol of 7,12‐dimethylbenz[a]anthrancene, which cannot be converted directly into a vicinal diol‐epoxide, was also active as a tumour‐initiating agent when applied to mouse skin.
Biochemical studies during aflatoxin B1‐induced liver damage in rats fed different levels of dietary protein
Authors: Mirmomeni M. H. , Suzangar M. , Wise A. , Messripour M. , Emami H.
Published: February 2007

Aflatoxin B1 has been fed for 6 months to young rats in low or high protein diets. In agreement with previous research, it was found that the high protein diet was associated with hyperplastic activity in the liver, of a type similar to that usually found in rats developing aflatoxin B1‐induced hepatoma. During the same period, negligible precancerous‐like changes were seen in the rats fed the low protein diet with aflatoxin B1. This model has been used to test the sensitivity of various liver function tests to the dietary‐induced difference in liver reaction to aflatoxin B1 feeding. The serum enzymes lactic dehydrogenase and alkaline phosphatase were considerably elevated in rats with precancerous‐like lesions, but the former was the most sensitive enzyme. Serum glutamate‐oxalate transaminase and serum glutamate‐pyruvate transaminase were both raised in the rats with precancerous‐like lesions, but much less so than lactic dehydrogenase and alkaline phosphatase. Urinary aflatoxin metabolites were also measured. Aflatoxin M1 and aflatoxin P1 were both found after feeding aflatoxin B1. During the feeding period, aflatoxin P1 excretion steadily increased, while aflatoxin M1 increased between the second and fourth months and then fell. In the first 4 months, rats fed a low protein diet tended to produce a lower ratio of aflatoxin M1 to aflatoxin P1 compared to the rats fed a high protein diet. At 6 months, the ratio decreased markedly, especially in the rats with the precancerous‐like lesions. It was concluded that lactic dehydrogenase, alkaline phosphatase, and the ratio of urinary excretion of aflatoxin M1 to aflatoxin P1 could be useful tests for inclusion in a diagnostic procedure for aflatoxin B1‐induced precancerous liver changes that might be expected in human studies.
The relationship between sister chromatid exchange, chromosome aberration and gene mutation induction by several reactive polycyclic hydrocarbon metabolites in cultured mammalian cells
Authors: Connell Jane R.
Published: February 2007

The ability of three ultimate metabolites of benzo(a)‐pyrene and of 7‐bromomethylbenz(a)anthracene to induce 8‐azaguanine mutants, sister‐chromatid exchanges and chromosome aberrations has been investigated. 7β,8α‐dihydroxy‐9α,10α‐epoxy‐7,8,9,10‐tetrahydrobenzo(a)pyrene was shown to be an extremely efficient inducer of both mutants and sister‐chromatid exchanges at 100% survival, whereas its geometrical isomer, 7β,8α‐dihydroxy‐9β,10β‐epoxy‐7,8,9,10‐tetrahydro‐benzo(a) pyrene and benzo(a)pyrene‐4,5‐oxide were comparatively weak. The potency of this compound, as both a mutagen and a sister‐chromatid exchange inducer, gives further evidence that it may be the important carcinogenic metabolite of benzo(a)pyrene. 7‐Bromomethylbenz(a)anthracene was a moderate mutagen and inducer of sister chromatid exchanges. Comparisons of the relative potencies of these four chemicals as inducers of both mutations and sister chromatid exchanges have indicated that these two phenomena are not directly related. The induction of sister chromatid exchanges also appears to be independent of the induction of chromosome aberrations.
Immunochemical characterization of tumor‐associated surface antigens on a moloney leukemia virus‐lymphoma, MBL‐2
Authors: Ng Ah‐Kau , McIntire K. Robert , Suzuki Seikichi , Aoki Tadao , Herberman Ronald B.
Published: February 2007

Tumor‐associated surface antigens (TASA)4 on a Moloney leukemia virus (M‐MuLV)‐induced lymphoma, MBL‐2, in C57BL/6 mice (B6) were characterized. The surface proteins of MBL‐2 cells were selectively radioiodinated and then extracted by Nonidet P40. The solubilized materials were then reacted with a variety of antisera: monospecific antisera to murine leukemia viral proteins (anti‐gp69/71, anti‐p30, anti‐p15, anti‐p12 and anti‐p10), sera from B6 which regressed murine sarcoma tumors induced by murine sarcoma virus (anti‐MSV) and a rabbit anti‐MBL‐2 antiserum. The resulting radioimmune precipitates were analyzed and compared in sodium dodecyl sulfate‐polyacryl‐amide gel electrophoresis (SDS‐PAGE). The following results were obtained. (1) Among all anti‐viral protein antisera tested only anti‐gp69/71 was active and detected a protein doublet of gp69/71 and its degradation fragments of 42,000 and 35,000 daltons. (2) Radioimmune precipitates prepared with anti‐MSV showed a SDS‐PAGE pattern similar to that seen with anti‐gp69/71. This result indicated that the surface antigen detected by the anti‐MSV serum on MBL‐2 tumor cell was probably a viral envelope antigen. (3) The rabbit anti‐MBL‐2 serum detected on the cell membrane an antigen of approximately 95,000 daltons which was tumor‐associated and did not appear to be related to virion components. The anti‐MBL‐2 serum still reacted with the 95,000 dalton antigen after absorption with disrupted M‐MuLV virus and with gp69/71 and p30 purified from the virus.
Female sex steroid receptors in normal, hyperplastic and carcinomatous endometrium. The relationship to serum steroid hormones and gonadotropins and changes during medroxyprogesterone acetate administration
Authors: Jänne O. , Kauppila A. , Kontula K. , Syrjälä P. , Vihko R.
Published: February 2007

Oestrogen and progestin receptors were measured from the cytosol fraction of normal, hyperplastic and carcinomatous human endometrium. Hyperplastic tissue contained the highest progestin receptor concentrations, followed by proliferative and secretory endometrium. Adenocarcinoma tissue was characterized by a lower progestin receptor content, which was further related to the degree of tumour differentiation with well‐differentiated carcinomas containing higher receptor levels than the poorly differentiated ones. There were no major differences in the oestrogen receptor values among the various tissue groups, except that poorly differentiated adenocarcinomas tended to have lower receptor levels than the others. The majority (80%) of adenocarcinomas contained both oestrogen and progestin receptors, in contrast to breast cancers where only half of the tumours simultaneously possessed the two receptors. There was no statistically significant correlation between serum oestradiol‐17β, progesterone, FSH or LH values and cytosol oestrogen or progesterone receptor concentrations in the various groups. Medroxyprogesterone acetate treatment for an average of 4 weeks significantly reduced the concentrations of cytosol oestrogen and progestin receptors in hyperplastic and carcinomatous tissue. Progestin receptor concentration declined to 10–20% of the initial value during this short‐term medroxyprogesterone acetate treatment. The depression in the cytosol receptor content may be detrimental for a beneficial hormone action to occur during a long‐term progestin treatment of endometrial carcinoma.
Establishment and characterization of human B‐lymphocytic lymphoma cell lines (balm‐3, ‐4 and ‐5): Intraclonal variation in the B‐cell differentiation stage
Authors: Lok Ming‐Swang , Koshiba Hirofumi , Han Tin , Abe Syuiti , Minowada Jun , Sandberg Avery A.
Published: February 2007

This study describes the establishment of three non‐Burkitt B‐lymphoma cell lines (BALM‐3, BALM‐4 and BALM‐5) originating from the pleural effusion of a patient with a poorly differentiated diffuse lymphocytic lymphoma. The cells of BALM‐3, ‐4 and ‐5 exhibited a number of properties which distinguish them from the usual B‐cell type lymphoblastoid cell lines. Thus, they lacked the Epstein‐Barr virus genome and had abnormal chromosome constitutions including a 14q+ marker. The presence of the identical surface immunoglobulin isotypes (γ and χ chain determinants), and la‐like B‐cell‐associated antigen in the cultured cells and in the “fresh” lymphoma cells in vivo was demonstrated. These findings strongly suggested that these cell lines have B‐cell characteristics and were derived from the original tumor cell population. BALM‐5 cells, however, showed somewhat different growth, cell surface marker profile and functional characteristics compared to those of BALM‐3, and ‐4 cells. These variations suggest that the BALM‐5 cells were probably at different stages of B‐cell maturation than those of BALM‐3 and ‐4, even though all three cell lines (established in three separate flasks) originated from the cells of the same pleural effusion of a lymphoma with monoclonal B‐cell characteristics.
Lung tumors from PuO2‐ZrO2 aerosol particles in syrian hamsters
Authors: Thomas R. G. , Smith D. M.
Published: February 2007

Syrian golden hamsters were given PuO2/ZrO2 particles via inhalation and/or Pu‐laden ZrO2 ceramic 10‐μm diameter microspheres lodged in the capillary bed of the lung. The mean initial lung burdens ranged from 8 nCi to 143 nCi for the six experimental groups of animals. Significant numbers of primary lung tumors (5–50% per group) were induced in those animals that received inhalation exposures. Additional alpha radiation administered via Pu‐laden intravenous microspheres had little or no effect on tumorigenesis or the production of non‐neoplastic, degenerative changes in the respiratory tract.
Mechanism of restriction of murine leukemia viruses varies between different strains of Fv‐1n mice
Authors: Benjers B. M. , Bassin R. H. , Rein A. , Gerwin B. I. , Duran‐Troise G.
Published: February 2007

The mechanism of Fv‐1 restriction in DBA/2 (Fv‐1n) mouse cells was investigated by quantitative infectious center assays employing a newly isolated continuous cell line. Titration of B‐tropic murine leukemia virus (MuLV) in DBA/2 cells showed two‐hit kinetics and, at sufficient multiplicities of infection (MOIs), the entire cell population could be productively infected with the restricted virus. Infection of DBA/2 cells with a single particle of B‐tropic (but not with N‐ or NB‐tropic) MuLV which had been inactivated at 43°C rendered the cells permissive to superinfection with B‐tropic MuLV. This effect was time‐dependent, the cells becoming permissive to B‐tropic MuLV by 3 h after the initial infection and regaining their restriction within 18 h. These findings, which are similar to our previous results on the infection of BALB/3T3 (Fv‐1b) cells with N‐tropic MuLV, indicate that two B‐tropic MuLV particles are required for successful infection of a DBA/2 cell in this non‐permissive system. These two particles appear to be functionally different: one temporarily overcomes or “abrogates” Fv‐1 restriction but need not replicate, while the second apparently undergoes a normal replication cycle. Two other Fv‐1n cell lines, NIH/3T3 and C3H 10T1/2, gave results which were not analogous to those obtained on DBA/2 cells. Even at high MOIs, only about 10–20% of NIH/3T3 or C3H 10T1/2 cells could be infected with B‐tropic MuLV. These quantitative differences in titration patterns indicate that NIH/3T3 and C3H 10T1/2 cells have different mechanisms of Fv‐1n restriction from that of DBA/2 cells, or, more likely, that they possess other restriction systems in addition to Fv‐1.
Active, specific immunotherapy of murine leukemia. II. Adjuvant effect of Corynebacterium parvum
Authors: Bartlett Gerald L. , Kreider John W.
Published: February 2007

We have previously shown that irradiated LSTRA cells (LX) were immunogenic and could prolong survival of mice bearing LSTRA tumors. This study demonstrated that addition of Corynebacterium parvum to the LX dramatically improved the strength of tumor immunity. In pretreatment‐challenge experiments, C. parvum augmented the immunogenicity of 106 LX given intradermally, with an optimum dose of 0.14–1.4 μg C. parvum per mouse. In therapy experiments (intraperitoneal vaccine treatment after tumor cell challenge), the therapeutic effect of 107 LX was improved by admixture of C. parvum, leading to a larger number of cured mice, permitting treatment of a larger challenge inoculum, and allowing later initiation of treatment than was possible with LX alone. Optimal dose of C. parvum for therapy was 1,400 μg per mouse. Presensitization to C. parvum or use of repeated vaccine injections did not further improve the therapeutic effect. Cure of tumor‐bearing mice by the mixed vaccine was tumor‐specific. These results suggest that C. parvum is a potent adjuvant for use in active, tumor‐specific immunotherapy.
Abortive expression of the epstein‐barr virus (EBV) cycle in a variety of EBV DNA‐containing cell lines, as reflected by nucleic acid hybridization In situ
Authors: Moar Martin H. , Klein George
Published: February 2007

A variety of Epstein‐Barr virus (EBV) DNA‐containing cell lines have been tested for the expression of the EBV‐associated antigens EBNA (nuclear antigen), EA (early antigen), and VCA (viral capsid antigen), and for the presence of cells containing disproportionate amounts of EBV DNA. The antigen tests utilized immunofluorescence and 125I‐labelled antibodies combined with auto‐radiography. EBV‐DNA was detected by in situ hybridization with 3H‐labelled EBV RNA complementary to P3HR‐1 EBV DNA (P‐EBVcRNA). The P‐EBV cRNA has been shown to represent the majority of the P3HR‐1 EBV DNA sequences. It was concluded that EBV DNA‐containing cell lines can be divided into those that express only EBNA, those that express EBNA and EA and those that express EBNA, EA and VCA and also contain cells that undergo disproportionate EBV DNA synthesis. Consequently, in some cell lines there is an abortive expression of the EBV cycle in that some cells spontaneously express EA but fail to continue further to viral DNA synthesis. A similar pattern can be found after experimental induction of the EBV cycle, suggesting that related mechanisms govern the spontaneous expression of the EBV cycle and the extent of its inducibility.
Glycophorin a as a cell surface marker of early erythroid differentiation in acute leukemia
Authors: Andersson Leif C. , Gahmberg Carl G. , Teerenhovi Lasse , Vuopio Pekka
Published: February 2007

We show here that the leukemic blast cells from three patients of a total of 15 subsequently diagnosed as having acute leukemia express on their surface the major red cell sialoglycoprotein, glycophorin A (GP‐A). This was demonstrated (1) by indirect immunofluorescence using rabbit anti GP‐A antiserum and (2) by immune precipitation of GP‐A from surface radiolabelled leukemic cells. Since GP‐A is exclusively present on erythroid cells and their precursors, these findings indicate that a higher proportion of the blast leukemias than previously recognized show features of early erythroid differentiation.
Luteinizing hormone‐releasing factor‐like immunoreactivity in islet cells and insulomas of the human pancreas
Authors: Wahlström T. , Seppälä M.
Published: February 2007

Luteinizing hormone‐releasing factor (LRF)‐like immunoreactivity was demonstrated by a three‐layer immunoperoxidase method in the islet cells of human pancreas and in the neoplastic cells of insulomas. Adenocarcinomas originating in the exocrine pancreas were LRF‐negative. The results demonstrate another hypothalamic peptide‐like material in the gastrointestinal tract, the biological role of which remains to be clarified.
Placental alkaline phosphatase, alphafetoprotein and carcinoembryonic antigen in testicular tumors. Tissue typing by means of cytologic smears
Authors: Wahren B. , Holmgren P. Å. , Stigbrand T.
Published: February 2007

Indirect immunofluorescence and radioimmuno‐assay with specific rabbit antisera demonstrated the occurrence of alphafetoprotein (AFP), carcino‐embryonic antigen (CEA) and placental alkaline phosphatase (PLAP) in primary testicular tumor cells. Embryonal carcinomas had AFP‐ and CEA‐containing cells, sometimes PLAP. PLAP and sometimes CEA were found in seminoma cells. Sera from patients with advanced non‐seminomatous tumors could contain any of these antigens or any combination of them. Sera from patients with seminomas had raised PLAP or CEA. PLAP appears to be a new marker for seminoma.
An assay for estradiol receptors using a staphylococcal protein‐a — estradiol antibody adsorbent
Authors: Ronchi Enrico , Porta Carla , di Fronzo Giovanni , Clerici Enrico
Published: February 2007

Antiestradiol antisera were raised in rabbits by immunization with a steroid‐protein conjugate Whole antisera and purified antiestradiol antibodies were reacted with heat‐killed and formalin‐fixed bacteria from the protein‐A‐bearing strain of Staphilococcus aureus (Cowan 1, NCTC 8530). The bacterial immunoadsorbent was used to estimate the estrogen‐receptor proteins contained in several specimens from human breast carcinoma. Since the affinity constant for estradiol of antiestradiol antibodies is about 108 M−1 while those for breast estrogen‐receptor complexes are about 109 to 1010 M−1, it is possible to remove the free steroid from a reaction mixture containing tissue cytosol, radiolabelled estradiol, and the antiestradiol bacterial adsorbent by pelleting the bacteria at low‐speed centrifugation. The radiolabelled estradiol molecules bound to their receptors remain in the supernatant and can be easily counted by liquid scintillation counting. The results obtained by this technique on specimens of human breast carcinomas compared more than satisfactorily with those obtained, on separated aliquots from the same specimens, by the dextran‐coated charcoal method, according to the EORTC group (1973). The versatility, specificity and stability of the antiestradiol bacterial immunoadsorbent recommend its use, rather than that of charcoal‐coated dextran and other non‐specific steroid adsorbents, in the mass screening of patients with breast carcinoma which could be amenable to hormonal therapy.
Embryo‐derived teratocarcinoma: I. The role of strain and gender in the control of teratocarcinogenesis
Authors: Solter D. , Dominis M. , Damjanov I.
Published: February 2007

The role of gender and genetic (strain‐specific) factors in the regulation of teratocarcinogenesis was studied by monitoring the outgrowth of benign and malignant embryo‐derived teratoid tumors, i.e., teratomas and teratocarcinomas in several mouse strains. Teratocarcinomas were produced in all mouse strains tested, but the ratio of teratoma to teratocarcinoma varied from one strain to another. A high yield of teratocarcinomas was obtained in A/J, BALB/cJ, DBA/2J, CBA/J and C3H/J mice, irrespective of the sex of the recipient. A low yield of teratocarcinomas was obtained in both male and female C57BL/6J and AKR/J recipients, and in 129/J female recipients. For all strains but 129/J and eventually AKR/J the sex of the recipients did not significantly affect the outgrowth of embryo‐derived tumors. These data suggest the existence of mouse strains with high and low permissiveness for embryo‐derived teratocarcinogenesis. The sex of the recipients may influence the yield of embryo‐derived teratocarcinomas in some mouse strains but is of no consequence in others.
Lung carcinoma induction in BD rats after a single intratracheal instillation of an arsenic‐containing pesticide mixture formerly used in vineyards
Authors: Ivankovic S. , Eisenbrand G. , Preussmann R.
Published: February 2007

A single intratracheal 0.1‐ml instillation of a calcium‐arsenate containing vineyard pesticide induced multi‐focal bronchogenic adenocarcinomas and bronchiolar‐alveolar‐cell carcinomas in nine out of 15 treated BD rats. This seems to be the first experimental confirmation of carcinogenicity of arsenic‐containing pesticides used formerly in vineyards.
Bioactivities and the effect of dilution on various milk‐borne murine mammary tumor viruses
Authors: Moore Dan H. , Vaidya Akhil B. , Long Carole A. , Manning Jarue S. , Heppner Gloria H. , Holben Jane A.
Published: February 2007

Infectivity titrations of milk‐borne murine mammary tumor virus (MuMTV) from different sources or prepared in different ways or stored for periods of time have been compared. Titration curves were in general reproducible for MuMTVs of different sources or handled in different ways and for different methods of measurement, such as hyperplastic alveolar nodule (HAN) development, tumor development, or MuMTV antigen secretion in third‐lactation milk. The curves had characteristic shapes with a low incidence of infection at low dilutions of milk, high incidences at intermediate dilutions, and low incidences at high dilutions. Infectivity incidences were unaffected by dilution over the range 10−2 to 10−5. The curves did not change appreciably with time of storage of milk at liquid N2 temperature for periods up to 3 years. Rate zonal fractionation of RIII milk gave zones with bioactivities which were not proportional to B‐particle content. Upon dilution, the bioactivity of Zone 3, rich in B particles, and Zone 5, poor in B particles, increased, while the bioactivity of all the other zones usually decreased with dilution. The low incidence of infection at low dilutions may have been due, in part, to an immune response of the inoculated mouse. Administration of inactivated virions 4 h prior to or with MuMTV inoculations gave some evidence in support of this hypothesis but the complexity of the bioassay system for MuMTV lends uncertainty to interpretation of results.
Expression of feline xenotropic RNA tumor virus in hybrids between permissive human and non‐permissive mouse cells
Authors: Edgell Cora‐Jean S. , Gazdar Adi F. , Minna John D.
Published: February 2007

Somatic cell hybrids were generated by fusing human (A549) cells, cloned after infection with the feline xenotropic CCC virus, to mouse (3T3) cells which are non‐permissive for this virus. Hybrid clones were found to be capable of expressing infectious virus. CCC virus expression, however, was regulated in the hybrid cells in such a way that 20–200 times less virus was released into the culture fluid than by the human parental line. Thus human permissiveness for this virus is co‐expressed with murine restriction. Markers for twenty human chromosomes were assayed in the hybrid clones. No single human chromosome was found to be essential and sufficient for CCC virus production, since none of them was consistently present or lost in virus‐positive and virus‐negative clones, respectively.
Betel quid chewing and oral cancer: Experimental studies on hamsters
Authors: Ranadive Kamal J. , Ranadive S. N. , Shivapurkar N. M. , Gothoskar S. V.
Published: February 2007

Betel quid ingredients — betel nut, betel leaf, lime, catechu and tobacco — were tested separately and in various combinations for carcinogenicity, using hamster cheek pouch as the experimental site. The four modes of administration used were (1) triweekly painting of the cheek pouch with aqueous extracts of test materials, (2) deposition of replaceable wax pellets containing the test material, (3) gelatin capsules containing the powdered material and (4) insertion of natural material into the pouch for trauma and direct exposure. Untreated controls and standard carcinogen DMBA‐treated controls were also maintained. A total of 317 young adult golden Syrian hamsters (Mesocricetus auratus) used for the experiments were killed in two age groups: 6–12 months and 13–24 months, only when signs of general debility were observed. In the untreated controls, animals were free of any malignancy. In the experimental series, various betel quid ingredient combinations under test induced both oral and gastric lesions ranging from massive atypia and precancerous lesions to frank carcinomas. Maximum lesions were observed in the groups receiving betel nut, lime and tobacco combinations and in the polyphenol fraction of betel nut containing major tannins. The mode of administration of test material resulted in distinct differences; tri‐weekly paintings giving oral lesions in the range of 22–23% and gastric lesions 39–48%; the same material given either through the replaceable gelatin capsule or in natural form induced 69% oral lesions and 63 to 82% gastric lesions. Overall evaluation of the data of all the four series confirms the potent carcinogenicity of betel nut, particularly its tannin‐containing polyphenolic fraction and its combination with lime and tobacco. Maximum oral lesions induced in the hamsters by continuous exposure to capsules and natural material, highlight the direct relationship of frequency of chewing in habitual chewers with oral carcinogenesis. The high incidence of gastric (forestomach) lesions invites special attention.
Cervical carcinoma: Detection of herpes simplex virus RNA in cells undergoing neoplastic change
Authors: McDougall James K. , Galloway Denise A. , Fenoglio Cecilia M.
Published: February 2007

3H‐HSV‐2 DNA has been hybridized in situ to frozen sectioned tissue from human cervical biopsies. RNA complementary to the virus‐specific probe was detected in cells undergoing pre‐malignant changes, but not in the cells of the fully developed squamous‐cell cancer.
Association of depressed postoperative lymphoproliferative responses to alloantigens with poor prognosis in patients with stage I lung cancer
Authors: Cannon G. B. , Dean J. H. , Herberman R. B. , Perlin E. , Reid J. , Miller C. , Lang N. P.
Published: February 2007

Thirty‐five patients with Stage I carcinoma of the lung were tested postoperatively to assess lympho‐proliferative responses. Depressed lymphocyte proliferation (LP) responses to alloantigen in the mixed leukocyte culture (MLC) as measured by the relative proliferation index (RPI) were associated with a significantly shorter disease‐free interval. In this group of patients, the immunologic responses predicted subsequent clinical course better than the TNM classification or the his‐tological type of the tumor, and therefore this procedure appears promising for improved staging of patients with early stages of lung cancer (stage I lung cancer and T1N0M0). The depressed response to alloantigen was a more sensitive discriminator of disease recurrence than PHA alone or even combined with PHA.