HUMAN CELL-MEDIATED BENZO(A)PYRENE CYTO-TOXICITY AND MUTAGENICITY IN HUMAN-DIPLOID FIBROBLASTS
- 1 January 1980
- journal article
- research article
- Vol. 40 (11) , 4070-4075
Abstract
A human epithelial cell-mediated cytotoxicity and mutagenicity assay system for [the carcinogen] benzo(a)pyrene [B(a)P] was developed with human fibroblasts as the target cells. Lethally X-irradiated human kidney carcinoma-derived epithelial cells had constant levels of B(a)P-metabolizing activity and were cocultivated with target human skin fibroblasts (XP12BE), which lack excision repair capability for B(a)P-DNA adducts. Under optimal assay conditions, the frequency of mutations to 6-thioguanine resistance induced in the target XP12BE cells by B(a)P and the binding of tritium-labeled B(a)P to DNA were concentration dependent. High-pressure liquid chromatography analysis of enzymatically degraded B(a)P-DNA adducts revealed 2 peaks: a major peak (82%) which cochromatographed with the guanosine adduct-standard synthesized from anti-isomeric-7,8-dihydro-diol-9,10-epoxide of B(a)P; and a minor peak (18%) which cochromatographed with the guanosine adduct-standard synthesized from syn-isomeric-7,8-diol-9,10-epoxide of B(a)P. Human liver carcinoma- and lung carcinoma-derived cell lines that were capable of metabolizing B(a)P proved equal to or better than the kidney carcinoma-derived cell line in producing cytotoxic B(a)P metabolites in the cell-mediated cytotoxicity assay with target XP12BE cells.This publication has 13 references indexed in Scilit:
- DNA excision-repair processes in human cells can eliminate the cytotoxic and mutagenic consequences of ultraviolet irradiationMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1979
- Mutagenesis of human cells by 3-methylcholanthreneMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1979
- Human bronchus-mediated mutagenesis of mammalian cells by carcinogenic polynuclear aromatic hydrocarbons.Proceedings of the National Academy of Sciences, 1978
- METABOLISM OF BENZO(A)PYRENE AND IDENTIFICATION OF MAJOR BENZO(A)PYRENE-DNA ADDUCTS IN CULTURED HUMAN COLON1978
- Some problems associated with the testing for environmental mutagens and a perspective for studies in “comparative mutagenesis”Mutation Research/Environmental Mutagenesis and Related Subjects, 1977
- Reactive derivatives of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene cause S1 nuclease sensitive sites in DNA and “uv-like” repairBiochemical and Biophysical Research Communications, 1977
- Cell-mediated mutagenesis in cultured Chinese hamster cells by carcinogenic polycyclic hydrocarbons: Nature and extent of the associated hydrocarbon-DNA reactionMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1977
- DIFFERENTIAL EXCISION FROM DNA OF C-8 AND N2 GUANOSINE ADDUCTS OF N-ACETYL-2-AMINOFLUORENE BY SINGLE STRAND-SPECIFIC ENDONUCLEASES1977
- The involvement of a diol‐epoxide in the metabolic activation of benzo(a)pyrene in human bronchial mucosa and in mouse skinInternational Journal of Cancer, 1976
- Short term screening tests for carcinogensNature, 1976