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Cytotoxic and mutagenic effects of specific carcinogen-DNA adducts in diploid human fibroblasts

Journal Article · · Environ. Health Perspect.; (United States)
DOI:https://doi.org/10.1289/ehp.8562145· OSTI ID:5457337
;
A comparison of the cytotoxicity and mutagenicity of a series of carcinogens in normal diploid human fibroblasts and in cells deficient in one or more DNA repair processes has provided insight into the specific DNA adduct(s) responsible for these biological effects. The carcinogens tested include ultraviolet radiation; reactive derivatives of structurally related aromatic amides; metabolites of benzo(a)pyrene; the simple alkylating agents N-methyl-N'-nitro-N-nitrosoguanidine and N-ethyl-N-nitrosourea; and aflatoxin B/sub 1/ dichloride, a model for the reactive 2,3-epoxide of aflatoxin B/sub 1/. Exponentially growing cells were exposed to agents and assayed for mutations and cell killing. Cells deficient in repair of particular DNA adducts or lesions proved more sensitive to the agent causing those lesions than did normally repairing cells. Many of the carcinogens were compared for their mutagenic and/or cytotoxic effect, not only as a function of dose administered, but also as a function of the initial number of adducts or photoproducts induced in DNA and the number remaining at critical times posttreatment. The results demonstrated a high correlation between the number of DNA lesions remaining unexcised at the time the DNA was replicated and frequency of mutations induced. Comparative studies of the frequency of UV-induced transformation of normal and repair-deficient cells showed this also to be true for transformation.
Research Organization:
Michigan State Univ., East Lansing
OSTI ID:
5457337
Journal Information:
Environ. Health Perspect.; (United States), Journal Name: Environ. Health Perspect.; (United States) Vol. 62; ISSN EVHPA
Country of Publication:
United States
Language:
English

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Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ALKYLATING AGENTS
ANIMAL CELLS
AROMATICS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CELL KILLING
CONNECTIVE TISSUE CELLS
DNA ADDUCTS
DNA REPAIR
ELECTROMAGNETIC RADIATION
FIBROBLASTS
GENETIC EFFECTS
GENETIC RADIATION EFFECTS
MUTATIONS
ORGANIC COMPOUNDS
RADIATION EFFECTS
RADIATIONS
RECOVERY
REPAIR
SOMATIC CELLS
TOXICITY
ULTRAVIOLET RADIATION
XP CELLS