Cytotoxic, mutagenic, and carcinogenic effects of energy-related agents in diploid human cells which differ in DNA repair capacity. Progress report, 1980-1983
The mechanisms of action of a series of energy-related chemical carcinogens to bring about cell killing, the induction of mutations, and the transformation of diploid human fibroblasts in culture were examined. Some of these studies have employed direct-acting compounds (reactive derivatives or metabolites of parent compounds) such as (+-)-7..beta..,8..cap alpha..-dihydroxy9..cap alpha.., 10..cap alpha..-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (anti BPDE), the 4,5-epoxide of benzo(a)pyrene(B(a)P 4,5-oxide), and aflatoxin B/sub 1/-dichloride (AFB/sub 1/-Cl/sub 2/). In other studies, human epithelial cell lines have served as source of the various metabolizing enzymes needed to convert parent compounds into reactive intermediates. We screened a series of 15 epithelial cell lines with unlimited lifespan (derived from various human carcinomas) for the ability to activate representative polycyclic aromatic hydrocarbons, aromatic amides, nitrogen heterocyclics, nitro samines, and/or aflatoxins. Candidate metabolizing cells were then combined with diploid human fibroblasts as target cells in a cell-mediated assay of the mutagenic and/or cytotoxic effect of particular energy-related chemical carcinogens, such as B(a)P, benzofluoranthenes, and dibenzo(c,g)carbazole. The number and kind of major DNA adducts formed in human cells by these chemicals were determined. Comparative studies of anti BPDE and B(a)P 4,5-oxide showed that in diploid human fibroblasts, both normal and DNA repair deficient, these agents do not differ significantly in mutagenic efficiency (per mean lethal event) or mutagenic effectiveness (per DNA adduct). In diploid Chinese hamster embryo fibroblasts anti BPDE had approx. 4-fold higher mutagenic efficiency than B(a)P 4,5-oxide in the latter cells. FA cells were significantly more sensitive than normal to killing by anti BPDE.
- Research Organization:
- Michigan State Univ., East Lansing (USA). Carcinogenesis Lab.
- DOE Contract Number:
- AC02-78EV04659
- OSTI ID:
- 5894896
- Report Number(s):
- DOE/EV/04659-T2; ON: DE83017082
- Resource Relation:
- Other Information: Microfiche only, copy does not permit paper copy reproduction
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANIMAL CELLS
SENSITIVITY
CARCINOGENS
CELL KILLING
MUTAGENESIS
BENZOPYRENE
CELL CULTURES
EXPERIMENTAL DATA
FIBROBLASTS
HAMSTERS
METABOLITES
ONCOGENIC TRANSFORMATIONS
ORGANIC NITROGEN COMPOUNDS
POLYCYCLIC AROMATIC HYDROCARBONS
SCREENING
ANIMALS
AROMATICS
CONDENSED AROMATICS
CONNECTIVE TISSUE CELLS
DATA
HYDROCARBONS
INFORMATION
MAMMALS
NUMERICAL DATA
ORGANIC COMPOUNDS
RODENTS
SOMATIC CELLS
VERTEBRATES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)