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Preferential binding of benzo(a)pyrene diol epoxide to linker DNA of human foreskin fibroblasts in S phase in the presence of benzamide

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
Addition of benzamide (BZ) at the onset of S phase inhibited expression of the neoplastic phenotype of human foreskin fibroblasts treated in vitro with (+/-)-7 ,8US -dihydroxy-9US ,10US -epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (B(a)P diol epoxide) in early S phase. Analysis of the specific B(a)P diol epoxide-DNA adducts revealed that ca. 65% of the total adducts in BZ and non-BZ carcinogen-treated cells was the B(a)P diol epoxide-deoxyguanine adduct. Limited micrococcal nuclease digestion of the early S phase nuclei from cells treated with B(a)P diol epoxide indicated that the carcinogen binds equally to linker and core DNA. However, when the cells were predominantly in S phase, in the presence of BZ, there was ca. three times more binding of B(a)P diol epoxide to the linker DNA compared to the core region. These data indicate that pretreatment of the cells with BZ at the onset of S phase established a preferential binding pattern in the linker DNA similar to that observed in the cells treated with B(a)P diol epoxide in G1 arrest.
Research Organization:
Ohio State Univ., Columbus
OSTI ID:
6335230
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 82:9; ISSN PNASA
Country of Publication:
United States
Language:
English