bluuebunny/crossref_metadata_2025 huggingface dataset:
Sites of integration of herpes simplex virus type‐2 thymidine kinase gene in human chromosomes
Authors: Kit Saul , Teitz Yael , Hazen Marion , Qavi Hamida
Published: February 2007

Isozyme analyses have been carried out to investigate the sites of integration of the herpes simplex type 2 (HSV‐2) thymidine kinase (TK) gene in biochemically transformed human [HeLa(BU25)/HSV‐2–6 Cl 4] cells. Extracts were prepared from He La (BU25)/HSV‐2–6 Cl 4 cells and from human—mouse somatic cell hybrids, which were obtained by fusing the biochemically transformed human cells with TK‐deficient mouse [LM(TK−)] cells, and were assayed for 26 isozymes representing markers for 20 human chromosomes. The isozyme analyses were generally consistent with previous karyotype studies, which revealed that the HSV‐2 TK gene was associated with an isochromosome, designated M13, formed from the short arm of human X chromosome in human—mouse hybrid lines HL/2 to HL/7, but with human chromosome 17 containing a trans‐location on the short arm in hybrid line HL/1 and its TK‐positive subclones. The isozyme analyses also indicated that the translocation on the short arm of human chromosome 17 in hybrid line HL/1 was probably derived from human chromosome 21. Hybrid line HL/1 and its TK‐positive subclones expressed a human—mouse heteropolymeric form of superoxide dismutase, a marker for human chromosome 21, but bromodeoxyuridine‐resistant, TK‐negative subclones of HL/1, and hybrid lines HL/3 to HL/6, which did not contain the modified chromosome 17, failed to express the human—mouse heteropolymeric form of superoxide dismutase. The human galactokinase isozyme, which is coded by a gene mapping close to the cytosol TK gene on human chromosome 17, was detected in extracts of TK‐positive HeLa S3, TK‐deficient HeLa(BU25), and biochemically transformed HeLa(BU25)/HSV‐2–6 Cl 4 cells, but not in extracts prepared from human—mouse hybrid line HL/1 and its subclones. These observations suggest that the gene for human galactokinase was either deleted or inactivated in HL/1 and its subclones, perhaps as a result of the translocation to chromosome 17.
Milky spots (taches laiteuses) as structures which trap asbestos in mesothelial layers and their significance in the pathogenesis of mesothelial neoplasia
Authors: Kanazawa Kyotaro , Roe Francis J. C. , Yamamoto Tadashi
Published: February 2007

The UICC standard sample of asbestos, crocidolite, was injected subcutaneously into the flanks of CBA/lac mice. Asbestos fibres were found in milky spots in the serosal cavities more than 442 days after the injection, in the form of either naked fibres or asbestos bodies. Milky spots were the only structure in which asbestos fibres were observed in the mesothelial layer. The fact that asbestos fibres were found in the liver, spleen, kidney, brain, etc., in addition to milky spots, suggested that they were transported by the blood stream throughout the body. This assumption was confirmed by the similar distribution of asbestos after intravenous administration. The vascular and cellular structure of milky spots is such that they are particularly likely to trap blood‐borne asbestos fibres. Hyperplastic changes were observed in milky spots after both subcutaneous and intravenous administration of asbestos in mice. The possible involvement of milky spots in the genesis of tumours of the mesothelium following exposure of animals to asbestos is discussed.
Enhancement by asbestos of oncogenesis by moloney murine sarcoma virus in CBA mice
Authors: Kanazawa Kyotaro , Yamamoto Tadashi , Yuasa Yasuhito
Published: February 2007

Five μg of finely ground crocidolite asbestos (UICC standard sample) were Injected intraper‐ itoneally into 3‐week‐old CBA mice, together with 105 FFU of Moloney murine sarcoma virus. Altogether 44 out of 61 mice (72.1%) so treated developed palpable intraperitoneal tumours, and half of these died of such tumours within 100 days. The same amount of quartr and carbon similarly administered gave lower tumour incidences, namely, 19.4% (3.2% fatal) and 11.9% (1.5% fatal) respectively. Only 1 out of 59 mice inoculated with the virus alone developed a palpable intraperitoneal tumour, and this regressed spontaneously within 10 days of its first appearance. No tumours were encountered in mice treated with either asbestos, quartz or carbon alone. All the neoplasms had the appearance, under the light microscope, of anaplastic sarcomas. Most of them were confined to the serosal surface of the abdominal cavity, although invasion of underlying tissues was observed in some of the animals that died. Electron microscopical examination of tumours revealed the presence of C‐type particles budding off from cellular surface. Some neoplastic cells showed characteristic features of mesothelial lining cells. The role of milky spots (taches laiteuses) in oncogenesis by asbestos and virus, especially in the induction of mesothelioma, is discussed.
Circulating levels and tissue localization of placental protein five (PP5) in pregnancy and tropho‐blastic disease: Absence of PP5 expression in the malignant trophoblast
Authors: Seppälä M. , Wahlström T. , Bohn H.
Published: February 2007

Placental protein five (PP5) was studied by radio‐immunoassay in 360 serum samples from 334 pregnant women, 96 serum samples from eight patients with trophoblastic disease, and 80 samples from apparently healthy women. PP5 was not found in the serum of healthy controls. It became detectable in maternal serum 8 weeks after the last menstrual period, and the levels progressively increased as pregnancy advanced. The highest levels (mean 26–29 ng/ml) were seen between weeks 37–39 of gestation. PP5 was rarely found in the serum of patients with trophoblastic disease. The first pretreatment samples of two patients with hydatidiform mole had PP5 levels of 0.6 and 2 ng/ml when the concentrations of human chorionic gonadotrophin (hCG) and pregnancy‐specific beta‐1‐glycoprotein (PSBG) were high, whereas the subsequent 17 samples were PP5‐negative. All seven samples from a patient with invasive mole and 70 samples from five patients with choriocarcinoma were PP5‐negative including those with high hCG and PSBG concentrations. Even a patient whose choriocarcinoma followed term pregnancy had no detectable PP5 in the serum. The occurrence of PP5 in tissue was studied by the three‐layer bridge immunoperoxidase method. PP5 was localized in the syncytiotrophoblast between 6 and 42 weeks of gestation, but the cytotrophoblast was PP5‐negative. The staining for PP5 was positive in all hydatidiform moles tested and in one of 10 cases of invasive mole. Choriocarcinomas were constantly PP5‐negative (6 cases). In the light of the biological role of PP5 as trypsin and plasmin inactivator its presence in normal and absence from malignant trophoblast suggests that PP5 may be involved in the regulation of trophoblastic invasiveness. The absence of PP5 expression in malignant trophoblastic disease makes it possible to use the serum PP5 measurement for the differential diagnosis of trophoblastic disease and normal pregnancy: in normal pregnancy the placental proteins PP5, hCG and PSBG are all present in serum 10 weeks after the last menstrual period, whereas in malignant trophoblastic disease hCG and PSBG are expressed in the absence of PP5.
Indirect leukocyte migration assay in patients with malignant melanoma
Authors: Morrison Lindsay J. , Cochran Alistair J. , Mackie Rona M. , Ross Catherine E. , Todd Gaye , Claire  , Garland G.
Published: February 2007

Leukocytes from 72 melanoma patients and 75 control donors were examined in a two‐stage (indirect) leukocyte migration assay, using formalin‐fixed melanoma cells (FMC) and control, normal or non‐melanoma tumour cells (FCC) as the source of antigen. Inhibitory supernatants were produced significantly more often by cultures of melanoma leukocytes and FMC than by melanoma leukocytes and FCC or control leukocytes and FMC or FCC. Reactive leukocytes were most frequently derived from stage II patients (65%), followed by stage I patients with tumour present (58%), stage III patients (29%) and stage I patients without detectable tumour (20%). The likelihood that a melanoma patient's leukocytes would react increased progressively with the number of different FMC preparations tested. A similar, though less steep increase in reactivity was seen with control donor leukocytes and different FMC preparations. No significant increase in reaction frequency was seen with melanoma or control leukocytes exposed to increasing numbers of different FCC preparations. Significant discrimination between melanoma patients' and control donors' leukocytes was achieved with FMC from both primary and metastatic tumours. Concordance of positivity or negativity was seen in 60% of concurrent one‐stage and two‐stage leukocyte migration assays.
Reciprocal 8;14 translocation in EBV‐negative B‐cell acute lymphocytic leukemia with burkitt‐type cells
Authors: Mitelman F. , Andersson‐Anvret M. , Brandt L. , Catovsky D. , Klein G. , Manolov G. , Manolova Y. , Mark‐Vendel E. , Nilsson P. G.
Published: February 2007

A cytogenetic study, including prophase‐prometaphase chromosome analysis, of a patient with EBV‐genome‐negative acute lymphocytic leukemia of B‐cell type with Burkitt‐type cells is presented. All bone‐marrow mitoses examined had a 14q + marker chromosome which was identified as a reciprocal 8;14 translocation of exactly the same type as in Burkitt's lymphoma.
Cell lines with spontaneous secretion of pregnancy‐associated α2‐globulin
Authors: Lundgren E. , Damber M. G. , Roos G. , von Schoultz B. , Stigbrand T. , Nilsson K. , Alexander J. J.
Published: February 2007

Pregnancy‐associated α2‐globulin (PA α2G) was quantitated by radioimmunoassay in culture media from 34 exponentially growing human cell lines. Only 8/34 cell lines produced PA α2G. The highest secretion was found in cell lines of histiocytic lymphoma origin while it was low in some carcinoma‐derived lines. The results may support an assumption that PAα2G is a normal cell product of B‐lymphoid, monocytic and epithelial cells but may also simply indicate that ectopic PAα2G production is especially common in tumors derived from such cells. The availability of PAα2G‐producing cell lines should facilitate studies of the immunoregulatory role of this protein.
Enhancement of carcinoembryonic antigen expression by interferon
Authors: Attallah Abdelfattah M. , Needy Charles F. , Noguchi Philip D. , Elisberg Bennett L.
Published: February 2007

Human interferon decreased DNA but not RNA synthesis in a human colon carcinoma cell line, WiDr; in addition, there was a two‐ to three‐fold increase in the expression of a tumor‐associated antigen, carcinoembryonic antigen. In contrast, interferon had no effect on a normal human diploid cell line, WI‐38. Thus, in addition to its anti‐cellular effect against tumor cells, interferon can also modulate tumor antigenicity.
Early detection of the CH1 murine lymphoma by tumor‐associated idiotype in the serum
Authors: Lanier Lewis L. , Babcock George F. , Lynes Michael A. , Haughton Geoffrey
Published: February 2007

In this report, we describe a sensitive C‐dependent2 51Cr release inhibition assay using anti‐idiotype antiserum which allows early detection of the CH1 murine B‐cell lymphoma by the presence of 19S tumor‐associated immunoglobulin in the serum. The assay is based on the finding that sera from mice bearing the CH1 lymphoma specifically inhibit C‐dependent 51Cr release from labelled CH1 cells in the presence of A‐Id serum. Groups of mice were injected ip with 102, 103, or 104 CH1 cells and serum samples were collected every other day until host death. Tumor‐specific idiotype was detectable as early as 8 days after a 104 CH1 tumor cell challenge and by 12–14 days in mice inoculated with 103 or 102 CH1 cells. The amount of idiotype increased in parallel with tumor burden and reached a peak titer just before host death In all cases, tumor‐associated idiotype was present in the serum time significantly prior to observation of a visible tumor mass (ca. day 20–28). In subsequent experiments, mice were inoculated with 104 CH1 cells and treated 16 days later with a single dose of melphalan (10 mg/kg), vincristine sulfate (0.75 mg/kg), or cyclophosphamide (100 mg/kg). Serum samples were taken from these animals and the level of serum idiotype was monitored. After M or VS drug therapy, the level of idiotype decreased in all mice, however host survival was not significantly prolonged. By contrast, mice treated with Cy survived significantly longer than untreated controls, and the serum idiotype titer in these mice decreased to undetectable levels from day 20–28. By day 37, idiotype was detectable again in the serum and all mice died of ascites tumor by day 44. The results of these experiments suggest that the presence of idiotype in the serum of a lymphoma‐bearing host may provide a marker which will allow early detection of tumor growth during periods of tumor remission induced by conventional chemotherapy.
Revertants of adenovirus type‐12‐transformed hamster cells have lost part of the viral genomes
Authors: Groneberg J. , Doerfler W.
Published: February 2007

The cell line T637 was derived from BHK21 cells (subline B3) by transformation with adenovirus type 12. The T637 cells contain multiple copies of the viral DNA, with different parts of the viral genomes being represented in unequal amounts. The persisting viral DNA has been shown in previous work to be covalently linked to cellular DNA. In the present report, the isolation and characterization of 18 morphological revertants of the T637 line are described. The T637 cells are round and epithelioid, the revertants are fibroblasts. The revertants arose spontaneously and could be enriched by letting the T637 culture grow to very high density; the T637 cells detached from the plastic surface, whereas the revertants stayed attached and could then be cloned. The morphological revertants of T637 cells differed from both the B3 and the T637 lines in a number of biological properties, such as saturation density, growth rate, agglutinability by plant lectins and uptake of low‐molecular‐weight compounds. The revertants were all T‐antigen negative, but reacted with anti‐LETS serum (antiserum against the large external transformation‐sensitive protein). The B3 and T637 cells were LETS‐negative. The revertants exhibited a pseudodiploid karyotype. All of the 18 revertants could be transplanted into 4‐week‐old Syrian hamsters, although most of the revertants grew less rapidly than the B3 cells. The patterns of integration of adenovirus type‐12 DNA were investigated using the DNA‐DNA hybridization technique of Southern. Some of the revertant lines (TR3, TR7, TR16, and F10) appeared to have lost almost all viral DNA sequences; the other revertant lines lacked several of the viral DNA sequences present in the T637 line. Upon superinfection of the T637 line and all of the revertants with adenovirus type 2 (Ad2), Ad2 replication was inhibited in T637 cells. In the revertants, however, Ad2 grew as efficiently or even more so than in the B3 line.
Growth of diploid, epstein‐barr virus‐carrying human lymphoblastoid cell lines heterotransplanted into nude mice under immunologically privileged conditions
Authors: Giovanella Beppino , Nilsson Kenneth , Zech Lore , Yim Ock , Klein George , Stehlin John S.
Published: February 2007

Human Epstein‐Barr virus‐carrying lymphoid cell lines which have been classified on the basis of studies on clonality and morphological, chromosomal and functional parameters as lymphoblastoid cell lines (LCL) of presumed non‐neoplastic origin were inoculated intracerebrally into nude mice. All eighteen of them grew, killing the host mice within 7 to 25 days, except for 2 which grew more slowly. At autopsy, the brain of the nudes was found to be invaded by infiltrating lymphomas. Sixteen of these lymphomas, when recultured in vitro, gave rise to cell lines with growth properties and morphology indistinguishable from those of the inoculated LCL. Chromosomal examinations showed that 3/7 cell lines injected, which grew as lymphomas in the brain, were still normal diploid on reexplantation whereas the remaining four had become aneuploid. Four lines derived from intracerebral lymphomas (2 diploid, 1 aneuploid and 1 untested) were inoculated subcutaneously into adult nude mice. None of them grew. When the corresponding four original LCL lines were inoculated subcutaneously into newborn nude mice, they grew rapidly, but failed to do so in newborn normal mice or intracerebrally in adult normal mice. One such line, U‐1450, was inoculated subcutaneously into adult nude mice treated with anti‐lymphocyte serum (ALS). Small nodules developed at the site of inoculation. From one nodule a cell line was cultured, 1450 ALSAD. It was morphologically indistinguishable from the line of origin. The lines obtained from nude mice inoculated with polyclonal LCL seem to have a restricted clonal representation, but were not monoclonal, as evidenced by analyses of their pattern of immunoglobulin synthesis.
Establishment, characterization and virus expression of cell lines derived from radiation‐ and virus‐induced lymphomas of C57BL/Ka mice
Authors: Lieberman Miriam , Decléve Alain , Ricciardi‐Castagnoli Paola , Boniver Jacques , Finn Olivera J. , Kaplan Henry S.
Published: February 2007

Permanent cell lines have been established in vitro from lymphoid tumors induced in C57BL/Ka mice by fractionated X‐irradiation or by inoculation of the radiation leukemia virus (RadLV). The cultured cells are lymphoblastic, replicate rapidly in vitro, and are tumorigenic in vivo. The cell surface markers Thy 1, Ly 1, Ly 2,3 and Gix are expressed by the lymphoid tumor cells in the mouse and persist in the corresponding cell lines; expression of the H‐2 and TL antigens is greatly reduced during in vitro passage, but is restored on in vivo transplantation. The cell lines derived from RadLV‐induced tumors (BL/VL lines) produce a virus population (RadLV/LTC) with the thymotropic and leukemogenic attributes of RadLV. Those derived from radiation‐induced, virus‐negative lymphomas (BL/RL lines) are initially devoid of MuLV expression, but frequently become spontaneous virus producers during in vitro cultivation.
A quantitative comparison of the mutagenicity of carcinogenic polycyclic hydrocarbon derivatives in cultured mammalian cells
Authors: Newbold R. F. , Brookes P. , Harvey R. G.
Published: February 2007

The mutagenicity of a series of reactive polycyclic hydrocarbon derivatives has been studied using Chinese hamster (V79) cells in culture and, as a mutational marker, resistance to the purine analogue 8‐azaguanine. The compounds were compared by relating mutation frequency to the dose applied (mutagenic effectiveness) to induced cytotoxicity (mutagenic efficiency) and to the extent of reaction of the hydrocarbon with DNA (absolute mutagenic efficiency). In each case anti‐benzo(a)pyrene (BP)—7,8 dihydrodiol‐9,10 oxide, the suspected ultimate carcinogenic form of benzo(a)pyrene, was by far the most potent of the compounds tested. Furthermore, the mutagenicity of the syn‐ and anti‐BP‐diolepoxide isomers correlated positively with their documented carcinogenic potency. Differences in mutagenic effectiveness are ascribed to predicted differences in the ability of each derivative to form a carbonium ion. Variations in mutagenic efficiency and absolute mutagenic efficiency were more difficult to explain. The latter findings are discussed in relation to the types of hydrocarbon‐DNA product obtained with each compound and also to the possibility of a variable cellular response to more subtle differences in the chemistry of the hydrocarbon‐DNA interaction.
Importance of a collagen substratum for stimulation of capillary endothelial cell proliferation by tumour angiogenesis factor
Authors: Schor Ana M. , Schor Seth L. , Kumar Shant
Published: February 2007

Tumour extracts were obtained from rat Walker 256 carcinoma and examined for the presence of tumour angiogenesis factor (TAF) in vivo before being used in tissue culture experiments. Capillary endothelial cells derived from cow brain white matter were used to study the effects of TAF‐containing tumour extracts on cell proliferation in vitro. The cells were grown on two types of substrata: (1) plastic tissue culture dishes and (2) hydrated gels made of rat tail tendon type I collagen. Human platelets or platelet‐released factors were introduced into the system because of the many inter‐relationships known to exist between platelets, collagen and endothelial cells. If trypsin was used during the preparation of TAT, the resulting batches stimulated endothelial cell proliferation only when the cells were growing on a collagen substratum and either platelets or platelet‐released factors were present in the growth medium. If incubation with trypsin was omitted from the TAF extraction procedure, the resulting batches stimulated cell growth both on plastic and on collagen. A synergistic interaction also occurred between these TAF‐containing tumour extracts and plateletreleased factors. This effect was always more marked when the cells were growing on collagen than when on plastic. These data suggest that the nature of the substratum affects the response of the endothelial cells to TAF and to platelet‐released factors.
Reversion of the transformed phenotype to the parental phenotype by subcultivation of X‐ray‐transformed C3H/10T1/2 cells at low cell density
Authors: Brouty‐Boyé Danièle , Gresser Ion , Baldwin Claire
Published: February 2007

Transformed cells induced by X‐irradiation of a stable contact‐inhibited line of C3H mouse embryo cells (10T½) display an altered morphology (fibroblastic), a decreased sensitivity to contact inhibition, a high cell saturation density, a decreased sensitivity to interferon and a capacity to form colonies in agar and malignant tumors in mice. Under certain experimental conditions, serial passage of transformed cells (from cloned lines) at low cell density (i.e., 400 cells per 25 cm2 flask) was accompanied by a reversion from the transformed phenotype to a phenotype characteristic of the parental untransformed 10T½ cells: epithelioid morphology, low cell saturation density, increased sensitivity to interferon and failure to form colonies in agarose or tumors in mice. The revertent phenotype was stable as long as these cells were passed at low cell density. Passage at high cell density, however, resulted in a back reversion to the transformed phenotype. When transformed cells were seeded at a much lower cell density, so that only a few colonies appeared per Petri dish, reversion to the parental phenotype occurred at the first passage and appeared stable. Back reversion was no longer observed even when these cells were passed at high cell density. The experimental results suggested that reversion of the transformed to the parental phenotype was not due to a selection of a pre‐existing population of cells with the parental phenotype but rather to a change in the phenotype of the entire cell population.
The value of a sensitive assay of carcino‐placental alkaline phosphatase (CPAP) in the follow‐up of gynecological cancers
Authors: Haije W. G. , Meerwaldt J. H. , Talerman A. , Kuipers Tj. , Baggerman L. , Teeuw A. H. , Van Pompe W. B. Der , van Driel Jolie
Published: February 2007

Using a sensitive enzyme immunoassay, carcinoplacental alkaline phosphatase (CPAP) was determined in sera of 1266 patients with gynecological cancers. All these patients were referred after initial surgical treatment elsewhere. There were 95 patients with evidence of disease at the time of the study and 1171 without evidence of disease. Of the 95 patients with active disease, 47 were treated for ovarian carcinoma, 36 for carcinoma of the cervix and 12 for endometrial carcinoma. Raised levels of CPAP were seen in 40% of patients with ovarian carcinoma, in 22% with carcinoma of the cervix and in 41% in the small group with endometrial carcinoma. In patients without evidence of disease, raised levels of CPAP were seen in 12% of patients with carcinoma of the cervix, in 6% of endometrial carcinoma and only in 2% of patients with carcinoma of the ovary. Therefore it was considered that in the latter group CPAP studies would prove of some value. In the group of patients with carcinoma of the ovary and evidence of disease, raised levels of CPAP were seen almost exclusively in patients with epithelial tumors. It is considered that CPAP may be of value as a tumor marker in this group of patients. When compared with CEA, CPAP tends to give fewer false positives and correlates better with the presence of disease.
Demonstration of chicken fetal antigen (CFA) on normal splenic lymphocytes, Marek's disease lymphoblastoid cell lines and other neoplasms
Authors: Murthy K. K. , Dietert R. R. , Calnek B. W.
Published: February 2007

Chicken fetal antigen (CFA) was detected on normal splenic lymphocytes and a direct relationship was observed between the percentage of CFA‐positive cells and the age of the donor. The fetal antigen was also detected on lymphoblastoid tumor cells and cell lines induced by known avian oncogenic viruses (Marek's disease virus and avian leukosis virus), and on spontaneously occurring adenocarcinoma cells. The fetal antigen appears to be distinct from Marek's disease tumor‐associated surface antigen.
Levels of mammary tumor virus proteins (MTVp27 AND MTVgp52) in the milk of low and high mammary cancer mouse strains of japanese origin compared with european and American strains
Authors: Imai Shunsuke , Hilgers Jo
Published: February 2007

A competition radioimmunoassay for purified MTV proteins, MTVp27gag and MTVgp52env, was applied to measure the amounts of these proteins in the milk of various mice of Japanese origin. The results were compared to those from European and American strains of high and low mammary cancer incidence. The sensitivity of detection for the assay was less than 1 ng viral protein per mg milk protein. The SL/NiA strain was positive for MTVp27 in the milk (10–100 ng/mg). Foster‐nursing of this strain on BALB/c mice did not lead to the disappearance of MTVp27 antigen expression, indicating that MTV in this strain is genetically transmitted. This strain was negative for MTVgp52. Various high mammary cancer strains had large amounts of MTV, invariably transmitted in milk, e.g. (1) FM/JmsA, (2) C57BL/6MsMtA, a strain selected for high mammary cancer incidence in Japan and maintained at the Aichi Cancer Center, (3) DD/Tbr. Levels of MTVp27 and MTVgp52 in the milk of these strains were comparable to those of the C3H/HeA, A/BrA and RIII/SeA. They were generally somewhat lower than in the BALB/cHeA strain foster‐nursed on high mammary cancer strain mice, such as A/BrA, RIII/SeA and FM/JmsA. Weight ratios of MTVp27 to MTVgp52 were usually 1:1 with the exception of the BALB/c foster A strain whose levels of MTVgp52 were comparatively high. BALB/cHeA strain milk itself showed some positivity for both MTV proteins at the borderline of detection (around 0.1 ng/mg protein). Mice of the C3H/HeA strain, foster‐nursed on C57BL/LiA mice, have much lower levels of MTVp27 (10–40 ng/mg) and MTVgp52 (8–50 ng/mg) than all the high mammary cancer strains. (C57BL × C3Hf)F1 hybrid mice had even less MTVp27 and gp52 in their milk than the C3Hf strain mice, permitting genetic analysis of the gene(s) for this suppression by the C57BL genotype.
Transplacental mutagenesis of products formed in the stomach of golden hamsters given sodium nitrite and morpholine
Authors: Inui Naomichi , Nishi Yoshisuke , Taketomi Masako , Mori Makiko , Yamamoto Miyako , Yamada Takashi , Tanimura Akio
Published: February 2007

Hamster embryos were exposed in utero to the action of sodium nitrite (NaNO2) and morpholine (Mo) administered simultaneously by stomach tube to the mothers on the 11th or 12th day of pregnancy. Embryo cells were examined for chromosomal aberrations, micronuclear formation, morphological or malignant transformation and drug resistance mutations. For detection of induced mutations, the embryo cells were cultured in normal medium for 72 h and then transferred to medium containing 10 or 20 μg/ml of 8‐azaguanine (8AG) or 1 mM ouabain (Oua). The number of 8AG‐, Oua‐resistant colonies was markedly increased after administration of NaNO2 and Mo. The embryonic fibroblasts also showed a markedly increased frequency of micronucleation and a slight increase in chromosome aberrations. This treatment also caused morphological or malignant transformation of fetal cells. After cultivation in vitro, cells from some transformed colonies produced tumors when inoculated into the cheek pouch of young golden hamsters. Orally administered N‐nitroso‐morpholine (N‐Mo), as a positive control, had the same transplacental biological actions on embryonic fibroblasts. However, transplacentally Mo alone was ineffective. A single administration of 500 mg/kg NaNO2 had only slight biological effects. N‐Mo was produced in the stomachs of animals treated simultaneously with NaNO2 and Mo. A small amount of a nitrosamine, N‐nitrosodimethylamine (DMN), was detected in the stomach after a single dose of NaNO2.
Alpha‐fetoprotein and γ‐glutamyltranspeptidase in mice. Effect of raf gene
Authors: Jalanko Hannu
Published: February 2007

The regulation of the high physiological level of serum alpha‐fetoprotein (AFP) in BALB/c/J mice was studied. Serum AFP concentration in 7‐ to 12‐week‐old BALB/c/J mice varied from 460 ng/ml up to 2,790 ng/ml and in other strains tested from 10 ng/ml to 400 ng/ml. In contrast to the difference in serum AFP level, activity of the fetal enzyme γ‐glutamyltranspeptidase (GGT) in the liver of BALB/c/J mice was similar to that found in other mice. In all newborn mice, the initially high GGT activity decreased almost 100‐fold during the first 10 days. The serum AFP concentration stayed relatively stable during this period. AFP decreased to the adult level between the 10th and 30th days. Partial hepatectomy and administration of carbon tetrachloride increased the serum AFP level in all mice. The elevation of AFP was 10 times higher in BALB/c/J mice than in mice with low basal AFP level. A slightly elevated GGT activity in the liver was observed in only 10 out of 40 mice after carbon tetrachloride treatment, but none of the mice after partial hepatectomy showed an elevation. These results suggest that the gene (“Raf” gene) controlling the reduced decrease of serum AFP level in young BALB/c/J mice enhances the “turning on” of production of AFP in the regenerating liver. This gene does not, however, control the expression of the other carcinofetal liver marker, GGT.
Epstein‐barr virus‐specific antibody‐dependent cellular cytotoxicity in patients with Burkitt's lymphoma
Authors: Pearson Gary R. , Qualtiere Louis F. , Klein George , Norin Torsten , Bal Inderjit Singh
Published: February 2007

Coded sera from 54 patients with African Burkitt's lymphoma (BL) were titrated for antibodies against an Epstein‐Barr virus (EBV)‐induced membrane antigen in the antibody‐dependent cellular cytotoxicity (ADCC) assay. The titers were then correlated with the progression of lymphoma growth following chemotherapy. In 74% of the patients with high ADCC titers (>3,840), lymphomas showed partial or complete regression following therapy. In the medium‐titered group (240–3,840), 36% of the lymphomas showed some response to therapy, while only 29% of the lymphomas in the low group (<240) responded to treatment. These preliminary results indicated that, as previously reported for patients with nasopharyngeal carcinoma, ADCC titers may be of prognostic value in patients with this EBV‐associated disease. In an attempt to determine the identity of the ADCC antigen, some of these sera were examined for antibody to the four major MA components so far identified in the membrane of EBV‐infected Raji cells. Sera with high ADCC titers in general contained antibody to the four major MA components, while low‐titered sera usually contained antibody to three or less of these proteins. There were exceptions to this pattern, however, indicating that the ADCC antigen might differ from the four EBV‐induced membrane components so far identified.
Growth requirements of human cervical epithelial cells in culture
Authors: Stanley Margaret A. , Parkinson E. Kenneth
Published: February 2007

Diploid cells derived from the portio surface of the cervix uteri of adult women can be grown in culture, from single cells. Ultrastructurally the colonies of growing cells show the features of stratified squamous epithelium and exhibit some of the differentiated characteristics of this epithelium in vivo. The successful serial cultivation of cervical epithelial cells, HCE, depends upon the presence of a non‐dividing fibroblast feeder layer which provides both attachment and growth factors for epithelial cells. Lethally irradiated Wi‐38, cervical fibroblasts or mouse fibroblast lines are all effective in promoting HCE colony formation and growth. Hydrocortisone and epidermal growth factor increase HCE colony size in the presence of a feeder cell layer. Culture lifetime was studied in five strains and ranged from 20–38 population doublings, with cells from older patients exhibiting a shorter culture life‐time.
Aryl hydrocarbon hydroxylase inducibility in lung cancer patients undergoing radiotherapy
Authors: Prasad Naresh , Prasad Rupi , Harrell James E. , Thornby John , Liem John H. , Hudgins Philip T. , Guinn Gene A.
Published: February 2007

Aryl hydrocarbon hydroxylase (AHH) inducibility was studied in cultured lymphocytes from 21 healthy control subjects and from 15 lung cancer patients selected for radiation therapy. AHH inducibility of the patients was measured prior to, during and at the end of radiation therapy. Four of 15 patients had high AHH inducibility. The remaining 11 patients had values comparable to the healthy controls. Cellular DNA and protein measurements of cultured lymphocytes were the same for patients and healthy controls. There was no significant difference in the percentage of lymphoblast formation and percentage of cell survival between the two groups. Radiation therapy reduces the number of lymphocytes in vivo and the amount of lymphoblast formation in vitro. AHH inducibility is significantly lowered by radiation in the patients who had very high inducibility at pre‐treatment level. DNA and protein contents of cultured lymphocytes did not change during radiation therapy.
Hepatitis b virus antigens in human primary hepatocellular carcinoma tissues
Authors: Goudeau A. , Maupas Ph. , Coursaget P. , Drucker J. , Chiron J. P. , Denis F. , Mar I. Diop
Published: February 2007

The presence of hepatitis B virus (HBV) antigens was examined in specimens of liver tissue obtained at necropsy from black Senegalese patients suffering from primary hepatocellular carcinoma (PHC). The results were correlated with markers of hepatitis B infection in serum. Hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) were sought for in 15 liver extracts. HBsAg was found in the liver in 10 of 12 cases with HBsAg‐positive serum. HBcAg was detected in three livers. The HBsAg was detected in seven of eight livers by immunofluorescence and orcein staining. HBsAG‐positive cells were mainly located in the peri‐tumoral cirrhotic tissue, although positive hepatocytes were also found in tumour nodules in liver from one of the patients. HBcAg was found in five of seven cases by immunofluorescence in hepatocytes of the cirrhotic areas. HBcAg fluorescence was primarily nuclear but, in some lobules, a patchy cytoplasmic fluorescence was observed. This suggests a cytoplasmnucleus pathway in the synthesis of the HBV core antigen. Electron microscopy was performed on two HBsAg‐ and HBcAg‐positive cases. Fibrillar and crystalline cytoplasmic inclusions were observed in tumour cells. In the same cells, 20–25 nm virus‐like particles were present in swollen cisternae of the endoplasmic reticulum.
Serum, pituitary and urine concentrations of prolactin and growth hormone in eight strains of mice with varying incidence of mammary tumors
Authors: Sinha Y. N. , Vlahakis G. , Vanderlaan W. P.
Published: February 2007

Eight inbred strains of mice with varying incidences of spontaneous mammary tumor were compared in regard to prolactin and growth hormone concentrations in sera, pituitary glands and urine. Serum prolactin was compared under basal conditions as well as after stimulation with perphenazine. Both hormones were measured with specific, homologous radioimmunoassays. Although some strains having a high incidence of mammary tumors had high levels of prolactin in sera, urine and pituitary glands, neither basal nor perphenazine‐induced serum concentrations showed a consistent pattern across mouse strains that correlated with the incidence of mammary tumors. Growth hormone levels in sera, pituitary glands and urine also had no characteristic pattern that applied to all strains studied. The ratio of prolactin depleted from the pituitary gland to prolactin detected in serum after perphenazine injection, which reflected the metabolic clearance rate of prolactin, was highest in two strains with a high incidence of mammary tumors and relatively lower in low‐tumor strains. These results suggest that if prolactin plays a part in mammary tumor development in mice, its mechanism varies with strains: while hyperprolactinemia may be the means in some strains, a peculiarity in the metabolism of the hormone may be more important in others.
Rauscher leukemia as a model for studies of marrow transplantation therapy: Results using syngeneic, allogeneic and hybrid donors
Authors: Okunewick James P. , Meredith Ruby F. , Brozovich Barbara J. , Seeman Paul R. , Schieb Ann L.
Published: February 2007

SJL/J mice with leukemia induced in their own cells by Rauscher leukemia virus were treated by marrow transplantation therapy. The results obtained using syngeneic, hybrid and two different allogeneic donors were compared. All types of donor tissue produced some degree of protection; the lowest was yielded by SJL/J cells and the highest by C57BL/10J. The incidence of leukemia recurrence after therapy varied with the donor strain used. The highest and earliest recurrence was seen with SJL/J donors. The use of leukemia‐resistant SJB10F1 hybrids resulted in protracted remissions followed by late relapse, which was possibly related to reemergence of host leukemogenic clones not previously eliminated by the pretransplant marrow ablation treatment. A distinctly different pattern of late deaths was seen with the use of allogeneic donors, suggesting a possible graft‐vs‐leukemia effect. Graft‐vs‐host (GvH) response was not evident following transplantation of either the hybrid or syngeneic marrow, as determined from studies using normal SJL/J mice as recipients. GvH disease was found using both types of allogeneic donors, C57BL/10J and 129/J. However, although both allogeneic donors were of the same histocompatibility type, H‐2b, they differed in the level of fatal GvH response induced when used as donors. This suggests the possibility of an influence of « minor » histocompatibility factors affecting GvH response incidence and animal survival. The similarities between the model and the results of treatment of human leukemia by marrow transplantation therapy are discussed, and the possible future use of the model to study means of achieving lower leukemia recurrence through better marrow ablation, and to study the question of whether there is a graft‐vs‐leukemia effect related to GvH response, is proposed.
Contribution of macrophages to interactions between tumor cells and other tissues assessed in an in vitro system
Authors: Maslow D. E. , Weiss L.
Published: February 2007

The modification of the tissues surrounding solid tumors is usually attributed exclusively to interactions between the normal tissues and the cancer cells in the tumor, in spite of the fact that tumors contain many different types of non‐cancer cells including macrophages. As an experimental model for some facets of the cellular interactions between tumor and normal tissues, we have assessed the individual contributions of macrophages and cancer cells to the differential inhibition of neural retina (NR) cell aggregation by co‐culturing NR cells with small numbers of macrophages or cancer cells alone, as well as with both natural (ascites tumors) and artificial mixtures. Cells from human colonic adeno‐carcinoma inhibited NR aggregation to a greater extent than normal colon mucosa. Aggregation of NR cells was inhibited by macrophages from mice and rats, and to a greater extent by cancer cell suspensions of mouse Ehrlich and rat Walker 256 lines from spinner culture or in the ascites form. Combinations of macrophages and cancer cells indicated that their inhibitory effects were neither additive nor synergistic. Cell‐free media from macrophages and cancer cell cultures were equally effective inhibitors of aggregation. The results suggest that the interaction between a malignant tumor and the surrounding normal tissue can be modified by cancer cells, tumor macrophages and their products.
In vivo induction of endogenous retroviruses in BALB/c mouse hepatocytes by successive treatments with carbon tetrachloride and bromodeoxyuridine
Authors: Ayukawa Hannah M. , Saltzburg Donna , Mukherjee Barid B.
Published: February 2007

The effects of bromodeoxyuridine (BrdUrd) incorporation into hepatocytes of carbon tetrachloride (CCl4)‐induced regenerating liver of BALB/c mice on the induction of endogenous retroviruses was examined. From the nucleic acid hybridization studies, the maximum levels of hybridization were obtained for both N‐ and X‐tropic BALB/c endogenous retrovirus specific [3H]‐cDNAs with liver RNA from animals receiving BrdUrd at 40 and 44 h post‐CCl4 treatment, and killed on the fourth day following BrdUrd injection. Media from NIH‐3T3 (Swiss mouse) and mink cell cultures, infected with liver homogenates from animals treated as above, gave significant levels of reverse transcriptase activity. The observations made in the present study show that BrdUrd incorporation into cell DNA can cause induction of both N‐ and X‐tropic endogenous retroviruses in BALB/c mouse hepatocytes in vivo, and such induction is probably a transient event.
Isolation of a SV40‐like papovavirus from a human glioblastoma
Authors: Scherneck Siegfried , Rudolph Michael , Geissler Erhard , Vogel Frank , Lübbe Liselotte , Wählte Helga , Nisch Gunther , Weickmann Friedrich , Zimmermann Wolfgang
Published: February 2007

A human glioblastoma multiforme (M27) tested in early cell cultures by indirect immunofluorescence staining showed SV40‐related tumor (T)‐antigen, 95% of the cells being positive. SV40‐related viral capsid (V)‐antigen was absent in all cells tested. Experiments to rescue this virus were performed by fusing M27 cells with CV‐I monkey cells, which were permissive for SV40, using polyethylene glycol (PEG) as fusion factor. We succeeded in isolating virus particles SV40‐GBM which electron microscopy showed to correspond in size and morphology to papovaviruses. Serological tests (hemagglutination, neutralization, fluorescent antibody) revealed that the virus is indistinguishable from SV40. Despite this apparent antigenic identity SV40‐GBM differs slightly from SV40 wild type. This virus can propagate and produce CPE in both CV‐I cells and primary fetal human kidney cells. Furthermore digestion of SV40‐GBM DNA with the HindII/III restriction endonucleases revealed minor differences compared with the SV40 DNA. Therefore the virus SV40‐GBM obtained from glioblastoma cells seems to be closely related to the SV40‐PML viruses described earlier.
Epstein‐barr virus specific IgA serum antibodies in nasopharyngeal and other respiratory carcinomas
Authors: Desgranges C. , De‐Thé G.
Published: February 2007

In order to better understand the relationship between IgA and IgG antibodies to Epstein‐Barr virus (EBV) in nasopharyngeal carcinoma (NPC), we analyzed 230 NPC sera but also a series of sera from patients with other carcinomas selected for their high EBV/IgG antibody titres. We were surprised to find that 21 out of 46 sera from bronchopulmonary carcinomas (BPC) and 6 out of 7 carcinomas of nasal fossae were IgA anti‐VCA positive, and 9 BPC sera and 5 nasal fossae sera were also positive for IgA anti‐EA. Bronchial undifferentiated small‐cell carcinomas may represent a particular group associated with high EBV profile.
The L1210 assay for immune complexes: Application in cancer patients and correlation with disease progress
Authors: Poskitt Paula K. F. , Poskitt Thomas R.
Published: February 2007

Immune complexes (ICs) were determined by the non‐complement‐dependent L1210 radioimmune assay on 132 serum samples collected from 53 patients with a variety of cancers. Both the mean IC levels and frequency of positive tests were significantly greater in cancer patients (mean = 96±100 μg/ml, 46% positive) than in a control group of 67 normal healthy blood donors (mean = 39±15, 3% positive). When cancer patients were assorted into groups by disease progress, those with large or progressing tumors had significantly higher mean values (136±129) and frequency of positives (75%) than those with small or regressing tumors (58±18, 22% positive). In lung cancer patients, IC levels showed a strong inverse correlation (rs = −0.903) with survival time in patients who died, and appeared to be a better prognostic indicator than performance status (Karnofsky scale) at time of diagnosis. Serial IC measurements taken on several patients showed a decrease in levels concomitant with a favorable response to cytoreductive therapy, sustained normal levels during periods of prolonged remission, and a rise to elevated levels with (and sometimes preceding) documentation of new metastases.
Antibody‐dependent cell‐mediated cytotoxicity against epstein‐barr virus membrane antigen in african Burkitt's lymphoma
Authors: Granlund David J. , Nkrumah Francis , Perkins I. Virginia , Biggar Robert J. , Levine Paul H. , Fuccillo David A.
Published: February 2007

Serial samples of sera from patients with African Burkitt's lymphoma were tested for antibody against Epstein‐Barr virus (EBV)‐specific membrane antigen (MA) by the antibody‐dependent cell‐mediated cytotoxicity assay (ADCC). Titers of patients in the long‐term survivor group were generally higher than those found in the sera of patients in the short‐term survivor group. Although ADCC titers to EBV‐MA were not useful in predicting which patients would relapse there was a definite relationship between ADCC titer and prognosis. The individual differences in ADCC titers in patients in remission may explain the variability of responses that have been reported in studies on serotherapy with remission plasma.