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D J Chen

Publications and source records attributed to D J Chen.

96 records · Page 6Linked to original sources
PubMed1982

Induction of 6-thioguanine-resistant mutations by rat-liver homogenate (S9)-activated promutagens in human embryonic skin fibroblasts.

Most normal human fibroblasts grown in culture do not metabolize promutagens/procarcinogens. Thus screening assays employing normal human fibroblasts have only been successful for direct-acting chemical mutagens and various radiations. In this report we describe a mutation assay (HGPRT locus) employing a normal human embryonic skin fibroblast and a rat-liver homogenate (S9) mixture. 3 model promutagens, benzo[a]pyrene (B[a]P), 3-methylcholanthrene (3MC), and dimethylnitrosamine (DMN) have been utilized in these studies. In addition to discussing conditions for optimizing the response of this assay, our results indicate that at constant amount of S9 protein concentration, there exists a linear correlation between mutagenicity and dose. At 50% survival, the mutant frequencies induced by B[a]P and 3MC (5 micrograms/ml) are 60 and 30 times the background mutant frequency, respectively. Similarly, at 50% survival, DMN (5 mg/ml) induced 6-TGr mutant frequencies are 25-fold over the background frequency. The increase in cytotoxicity resulting from exposure of cells to these 'activated' chemicals is also a linear dose response. At high S9 concentrations a deactivation or detoxification phenomenon occurs. However, the mutagenic efficiency of S9-activated chemicals when plotted as the number of induced mutations versus log survival is unaffected by the deactivating capacity of S9 proteins. This study demonstrates a quantitative mutation assay using an early passage human culture with an exogenous rat-liver microsomal preparation providing activating enzymes.

Animals↗
PubMed1982

Genotoxicity induced in cultured Chinese hamster cells exposed to natural or synthetic crude oils and near ultraviolet light.

Cultured Chinese hamster ovary (CHO) cells were incubated with dilutions of natural or synthetic crude oils and subsequently exposed to near ultraviolet light (NUV). Although the magnitude of photo-induced cytotoxicity in CHO was essentially independent of the source of the oil (within a factor of two), two shale oils were exceptionally high in photo-induced mutagenic activity eliciting a response 10-12 times the observed natural background mutation frequency. Other shale oils, natural crude oils and a solvent refined coal medium distillate blend were weaker or negative in photo-induced mutagenic activity. Hydrotreatment of a photoactive shale oil, although eliminating the mutagenic potential, did not reduce the oil's cytotoxic potential.

Animals↗
PubMed1982

Genotoxic effects of sunlight-activated waste water in cultured mammalian cells.

Cultured Chinese hamster ovary cells were incubated with dilutions of an oil shale retort process water and exposed to nautral sunlight. An enhancement of sevenfold to ninefold was seen in photoinduced cytotoxicity (by a colony-forming assay) and mutagenicity [at the hypoxanthine phosphoribosyltransferase (HPRT) locus] for cells pretreated with the process water compared to effects seen in cells exposed to sunlight only. Significant photoinduced cytotoxicity was also observed in cultured human skin fibroblasts when exposed to the process water before being exposed to near UV (NUV) radiation. The mutation frequencies (determined for the HPRT locus) induced by the process water and NUV radiation were as great as those frequencies seen for far UV light alone. Increases in genotoxicity were observed in excision repair-deficient xeroderma pigmentosum skin fibroblasts when compared to the responses seen in normal cells. Risks to health resulting from the phototransformation of these oil shale retort process waste waters are unassessed at this time.

Animals↗
PubMed1981

Cytotoxic and mutagenic properties of shale oil byproducts. I. Activation of retort process waters with near ultraviolet light.

Cultured Chinese hamster ovary (CHO) cells were exposed to dilutions of shale oil retort process waters obtained from three different retorting processes located in the Green River oil shale formations in the western part of the United States. Although the intensity of the response was dictated by thd process water used, all induced a cytotoxic (reduction in colony-forming ability) and mutagenic (induced at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus) response in cells pretreated with dilutions of the waters and subsequent exposure to near ultraviolet light (NUV). Combinations of process water plus NUV yielded mutation frequencies as great as 50% that witnessed for the mutation frequency induced by the potent carcinogen far ultraviolet light. NUV alone was nontoxic and nonmutagenic at the doses of radiation used. Exposure of CHO cells in the dark to nontoxic dilutions of the process waters resulted in small but significant increases in 6-thioguanine resistant mutants. (1-2 time background rates). The biological consequences resulting from the disposal of retort process waters into the delicate environment present in this oil shale region could be further complicated by this photoactivating process.

Animals↗
PubMedDate not supplied

Functional complementation of the radiation-sensitive mutant M10 cell line by human chromosome 5.

The mouse lymphoma (L5178Y) cell mutant M10 is defective in rejoining DNA double-strand breaks and is hypersensitive to ionizing radiation. The introduction of human chromosome 5 into M10 cells by microcell mediated chromosome transfer complemented the ionizing-radiation hypersensitivity defect of this cell line. The presence of chromosome 5 in the microcell hybrids was shown using PCR with chromosome-specific primers and fluorescence in situ hybridization. From this data we conclude that the gene that corrects the radiation hypersensitivity of M10 cells is located on chromosome 5 and tentatively assigned to the 5q14 to 5pter region. We designate this gene XRCC4L.

Animals↗