Effects of exposure to benzo(a)pyrene-diol-epoxide-I on DNA replication in C3H 10T1/2 cells

Conference · Thu May 01 04:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:7164038

Paules, R S; Mass, M J; Cordeiro-Stone, M; Foirier, M C; Yuspa, S H; Kaufman, D G

DNA synthesis during exposure to chemical carcinogens facilitates the neoplastic transformation of cells. In order to investigate the effects of carcinogen exposure on DNA replication, methodology has been developed for the quantitative localization of sites of modification in DNA. They used rabbit antibodies that were specific in their recognition of the deoxyguanosine adduct formed upon exposure of DNA to benzo(a)pyrene-diol-epoxide-I (BPDE-I). The antibody bound to carcinogen-DNA adducts were visualized by electron microscopy techniques. This quantitative methodology was utilized in studies of the effects of exposure to BPDE-I of synchronized populations of C3H 10T1/2 clone 8 mouse fibroblasts. Cells in mid-S phase were very sensitive to the cytotoxic effects of exposure to BPDE-I. Levels of BPDE-I that produced 0.8 and 2 fmoles of adducts per ..mu..g of DNA resulted in 50% and 1% survival, respectively. DNA synthesis rates were reduced to 32% and 13% of control levels, by 90 min, in cells containing an average of 19 and 38 fmoles of BPDE-I adducts per ..mu..g of DNA. DNA replication fork structures with antibodies bound to BPDE-I-DNA adducts were analyzed by electron microscopy. The highest carcinogen binding was found in close proximity to the fork junction. This preferential adduction was found to increase with time following carcinogen exposure.

• Research Organization: Univ. of North Carolina School of Medicine, Chapel Hill
• OSTI ID: 7164038
• Report Number(s): CONF-8606151-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:6
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ANIMAL CELLS
ANIMALS
ANTIBODIES
AROMATICS
BENZOPYRENE
BIOLOGICAL EFFECTS
CARCINOGENS
CONDENSED AROMATICS
CONNECTIVE TISSUE CELLS
DNA
DNA ADDUCTS
DNA REPLICATION
ELECTRON MICROSCOPY
FIBROBLASTS
GENETIC EFFECTS
HYDROCARBONS
MAMMALS
MICE
MICROSCOPY
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
ORGANIC COMPOUNDS
RABBITS
RODENTS
SENSITIVITY
SOMATIC CELLS
VERTEBRATES