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W F Benedict

Publications and source records attributed to W F Benedict.

At least 109 records · Page 6Linked to original sources
PubMed1983

High-density lipoproteins decrease both binding of a polynuclear aromatic hydrocarbon carcinogen to DNA and carcinogen-initiated cell transformation.

Lipophilic carcinogens partition into the three major classes of lipoproteins potentially present in serum used as a medium supplement for cell culture. Different serum lots sequester differing quantities of the procarcinogen benzo[a]pyrene, dependent on the serum lipoprotein concentrations. In the presence of high-density lipoproteins a mutagenic benzo[a]pyrene metabolite was bound to cellular DNA at decreased levels when compared to cells exposed to the mutagen in the absence of high-density lipoproteins. Fetal calf serum with low levels of lipoproteins, specifically, high-density lipoproteins, is associated with efficient methylcholanthrene-initiated transformation of C3H/10T1/2 cells, while calf serum with a significant concentration of high-density lipoproteins requires up to a 500% increase in methylcholanthrene concentration to achieve similar levels of transformation in this mouse embryo cell line. When concentrated serum lipoproteins or purified HDL were added to fetal calf serum containing MCA at 1 microgram/ml, the C3H/10T1/2 transformation frequency was decreased compared to the transformation frequency achieved in the presence of 1 microgram/ml of MCA in fetal calf serum without supplementation. The results suggest that high-density lipoprotein partitioning of lipophilic polynuclear aromatic hydrocarbon mutagens from the cell culture medium may effectively reduce the concentration of carcinogen available for interaction with cellular DNA in vitro, which, in turn, may be associated with decreased carcinogen-induced transformation of cells.

Animals↗
PubMed1983

Nonrandom chromosomal changes in untreated retinoblastomas.

The karyotypic patterns of 15 retinoblastomas were examined. Five tumors were found to have two distinct stem lines and, therefore, the chromosomal patterns of 20 tumor cell lines are reported. Three nonrandom chromosomal changes, namely, a loss of a chromosome #13, the presence of an i(6p), or a trisomy of 1q were observed. The potential importance of these chromosomal changes in tumor development is discussed, particularly the loss of a chromosome #13 or the gain of an i(6p). At least one of the three chromosomal changes was found in 75% of the tumor lines analyzed.

Aneuploidy↗
PubMed1983

Comparison of mutagenicity and induction of sister chromatid exchange in Chinese hamster cells exposed to hematoporphyrin derivative photoradiation, ionizing radiation, or ultraviolet radiation.

Cell culture studies have been performed to compare the mutagenic potential and the induction of sister chromatid exchanges for hematoporphyrin derivative photoradiation, ionizing radiation, and UV radiation. The mutation frequency in Chinese hamster ovary cells at the hypoxanthine-guanine phosphoribosyltransferase locus was measured using resistance to 6-thioguanine. Phenotypic expression time prior to mutation selection was also examined. Treatment with either X-rays or UV was effective in producing mutants resistant to 6-thioguanine, but treatment with hematoporphyrin derivative photoradiation (at comparable toxicity levels) did not induce any mutagenic activity above background levels. The hematoporphyrin derivative incubation and photosensitization conditions used in this study did induce sister chromatid exchanges at frequencies comparable to those induced by X-rays but at lower frequencies than for UV treatments.

Animals↗
PubMed1982

Tissue distribution of 3H-hematoporphyrin derivative in athymic "nude" mice heterotransplanted with human retinoblastoma.

Quantitative uptake levels of tritium-labeled hematoporphyrin derivative (3H-HpD) have been obtained for normal and malignant tissue of athymic "nude" mice heterotransplanted intraocularly with human retinoblastoma. It was determined that eyes with tumor accumulated higher levels of 3H-HpD than those in control eyes. In addition, an improved therapeutic retention ratio of the drug (eyes with tumor compared with control eyes) was obtained at extended time intervals after administration.

Animals↗
PubMed1982

Differences in anchorage-dependent growth and tumorigenicities between transformed C3H/10T 1/2 cells with morphologies that are or are not reverted to a normal phenotype by ascorbic acid.

C3H/10T 1/2 mouse embryo cells were transformed with 3-methylcholanthrene. Several type III morphologically transformed cell lines were selected with morphologies that either could or could not be reverted back to normal at passage 1 by daily addition of ascorbic acid (1 or 5 microgram/ml). Those transformed cell lines with morphologies that could be caused to revert to normal did not produce colonies in agarose or tumors in nude mice at early passages. Such transformed cell lines at later passages all formed colonies in agarose, but only 2 of 8 lines produced tumors at any passage tested. Subsequently, clones of transformed cells from each cell line have been isolated which are tumorigenic. In contrast, the transformed cell lines which were unresponsive to ascorbic acid at passage 1 were able to form colonies and to produce tumors in early passages. The reversion of the transformed morphology by ascorbic acid is apparently not caused by cytotoxicity since no cell kill was observed following exposure to ascorbate in any newly transformed cell lines at the concentrations used. Thus, the use of ascorbic acid allowed morphologically transformed cell lines to be isolated which appeared to be at different stages in the progression of an initiated cell from a morphologically transformed cell to a highly tumorigenic one. These studies also suggest that low concentrations of ascorbic acid in C3H/10T 1/2/CL8 cells can be effective in suppressing oncogenic progression only prior to a stage where an initiated cell achieves the capacity to grow in semisolid medium and to produce tumors in immunosuppressed animals. The importance of these cell lines for elucidating key changes required for the promotion and/or progression of cells to a tumorigenic phenotype is also presented.

Animals↗
PubMed1980

The nude mouse model for human retinoblastoma: a system for evaluation of retinoblastoma therapy.

We have critically examined the nude mouse model for human retinoblastoma to determine whether or not characteristics found in the parent tumor are retained in the mouse. We have demonstrated that most tumors grown in the anterior chamber of the nude mouse maintain a similar karyotype, show the same degree of differentiation and develop an adequate tumor blood supply when compared to the primary tumor from which they were obtained. Because of these findings, we suggest that this model may be particularly useful for evaluating new methods or combinations of treatment for human retinoblastoma.

Animals↗
PubMed1980

Tumor regression of human retinoblastoma in the nude mouse following photoradiation therapy: a preliminary report.

Retinoblastoma is the most common malignant intraocular neoplasm of childhood. Enucleation of both eyes is necessary in some advanced cases where radiotherpy and other modalities of treatment have failed. We present in this paper our initial observation that photoradiation therapy (the combination of the photosensitizing drug, hematoporphyrin derivative, and red light) produces marked tumor cytotoxicity in human retinoblastoma heterotransplanted into the anterior chamber of the nude mouse eye.

Animals↗
PubMed1980

Anchorage independent growth and plasminogen activator production by bovine endothelial cells.

Endothelial cells obtained from the aortae of 1- to 2-d-old calves were cloned at high efficiency using fibrin-coated dishes. Primary cultures as well as clones derived from them produced high fibrinolytic activity when grown on 125I-fibrin-coated dishes which was 90% dependent upon the presence of plasminogen. High plasminogen-dependent proteolytic activity was also demonstrated in endothelial cell lysates and in the culture medium of the cells. The production and secretion of the plasminogen activator(s) were found to increase during the log phase of cell growth and to reach a maximum level at confluence. These endothelial cells exhibited morphological phenotypes comparable to those of transformed cells when grown in the presence of acid-treated fetal calf, dog, or human serum. Furthermore, they demonstrated anchorage independent growth, and large colonies were formed in semisolid media. Spontaneous neoplastic transformation of these cells was excluded by karyotypic analysis, lack of tumorigenicity in athymic nude mice, and limited lifespan in culture. Cell clones isolated from colonies grown in agarose demonstrated the same growth characteristics and proteolytic activity as before plating in agarose. High fibrinolytic activity, morphological changes in the appropriate serum, and growth in semisolid media may therefore be indicative of the migratory and/or invasive capacity of both nontransformed endothelial cells as well as tumor cells.

Agar↗
PubMed1980

Variability in DNA distributions of human neuroblastomas after cyclophosphamide.

Major changes in DNA distributions of two human neuroblastoma cell lines growing in vitro and in athymic nude mice occurred after treatment with cyclophosphamide. Pulse treatment of LA-N-1 cells in vitro with liver S-9-activated cyclophosphamide (10 micrograms/ml) caused approximately 50% cytotoxicity; flow microfluorometric analysis of surviving cells demonstrated an increased proportion of G2 + M cells and a decreased proportion of G1 cells, particularly at 48 hrs. Even though LA-N-1 tumors in nude mice did not regress after one dose of cyclophosphamide (250 mg/kg), the percent of G2 + M cells increased and the percent of G1 cells decreased 4-6 days after treatment; the percent of cells in S increased at 2 and again at 8 days. SK-N-MC cells were affected differently by cyclophosphamide. Pulse treatment of these cells in vitro with liver S-9-activated cyclophosphamide caused greater than 85% cytotoxicity and nearly complete elimination of cells in G2 + M at 24 and 48 hrs. Likewise, SK-N-MC tumors in nude mice regressed greater than 50% after cyclophosphamide, and the proportion of G2 + M cells decreased markedly 2-6 days after therapy. We conclude that cyclophosphamide can have different cytotoxic and cytokinetic effects on neuroblastomas. In addition, marked cytokinetic effects may occur even though changes in tumor size are minimal or not detectable.

Animals↗
PubMed1979

C-type RNA virus from hamster cells transformed in vitro by 1-B-D-arabinofuranosylcytosine.

Evidence of type-C RNA viral activity in fetal hamster cells transformed in vitro by 1-B-D-arabinofuranosylcytosine (ara-C) after at least one in vivo passage is described. The virus possesses properties typical of other type-C RNA viruses, such as: a) morphology as determined with the electron microscope, b) presence of 70S RNA, c) enhanced expression following treatment with halogenated pyrimidines, d) group specific antigens of hamster type, and e) a buoyant density of 1.15 g per cm3. However, the virus particles are deficient in RNA-dependent DNA polymerase activity under conditions that easily detect Rauscher Leukemia virus and will infect neither hamster, rat, mouse, human nor rabbit cells. The possible role of this virus in chemical carcinogenesis of cultured hamster fetal cells is discussed.

Animals↗
PubMed1979

Biological activity of tobacco smoke and tobacco smoke-related chemicals.

Exposure to whole cigarette smoke from reference cigarettes results in the prompt (peak activity is 6 hrs), but fairly weak (similar to 2 fold), induction of murine pulmonary microsomal monooxygenase activity. This activity can be detected by using as substrates either benzo(a)pyrene or ethoxyresorufin, and can be inhibited by treatment with cycloheximide or actinomycin D. Unlike the induction of pulmonary monooxygenases following intratracheal administration of 3-methylcholanthrene, these cigarette smoke-induced increases were not unequivocally linked to the Ah locus. Whole smoke condensate and fractions derived from these condensates can; a) induce pulmonary monooxygenase activity, b) inhibit benzo(a)pyrene metabolism in vitro, c) be metabolized to forms mutagenic to Salmonella typhimurium tester strains TA153, or TA98, d) transform C3H 10T1/2 cells in vitro, and e) enhance the carcinogenicity of benzo(a)pyrene in murine pulmonary tissue. A potentially important observation is that whereas hepatic tissue is capable of activating whole cigarette smoke condensate to mutagenic forms in vitro, murine pulmonary tissue does not seem capable of such activation. Although these pulmonary-derived tissue homogenates have significant AHH activity and can metabolize Aflatoxin B1, 2-aminofluorene and 7, 8-dihydro-7,8-dihydroxybenzo(a)pyrene to mutagenic forms, these homogenates fail to activate both cigarette smoke condensate and the pro-mutagen, 6-aminochrysene. These results are discussed with reference to the concept that whole cigarette smoke may be both a potential "initiator" and "promotor" of lung cancer in mice, and that this latter property may be the most important in determining cancer risk.

Animals↗
PubMed1979

Correlation between prognosis and bone marrow chromosomal patterns in children with acute nonlymphocytic leukemia: similarities and differences compared to adults.

The chromosomal complement of 28 children with the diagnosis of acute nonlymphocytic leukemia (ANLL) were examined. An abnormal cytogenetic pattern was found in 50% of these patients, which is similar to the results in adults with ANLL. Unlike the reports in adult patients, however, no specific chromosomal changes were found. This observation may imply that the etiology and mechanisms by which abnormal clones develop in ANLL could differ significantly between children and adults. Those patients with chromosomal abnormalities in their initial bone marrow sample had a median survival of 7.1 mo, whereas those with a normal diploid pattern in their bone marrow had a median survival of 20.5 mo (1-sided, p = 0.04). If all metaphases were abnormal, the median survival was only 3 mo.

Adolescent↗
PubMed1979

Production of sister chromatid exchanges by various cancer chemotherapeutic agents.

Various cancer chemotherapeutic agents have been examined for their ability to produce increases in sister chromatid exchanges. Those agents which had been shown previously to produce oncogenic transformation as well as chromosomal breaks also showed significant increases in sister chromatid exchanges. Those drugs which had not been shown to be oncogenic or clastogenic in cell culture produced no increases in sister chromatid exchanges. In general, concentrations which yielded increases in sister chromatid exchanges were considerably lower than those which had been shown previously to produce oncogenic transformation and chromosomal breakage. This was particularly true for the alkylating agents. Thus, we concur that examining increases in the production of sister chromatid exchanges may be an additional sensitive method for detecting potential mutagenic and/or oncogenic agents in our environment.

Animals↗