Preferential binding of benzo[a]pyrene diol epoxide to the linker DNA of human foreskin fibroblasts in S phase in the presence of benzamide.
Addition of benzamide (BZ) at the onset of S phase inhibited expression of the neoplastic phenotype in human foreskin fibroblasts treated in vitro with (+/-)-7 alpha,8 beta-dihydroxy-9 beta,10 beta-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. The confluent cells in G1 cell arrest treated only with B[a]P diol epoxide also bound the carcinogen preferentially to the linker 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[alpha]P diol epoxide in G1 arrest.
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D001549:Benzamides / Q000494:pharmacology*; D001580:Benzopyrenes / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007399:Interphase; D012867:Skin / Q000378:metabolism
D001549:Benzamides; D001580:Benzopyrenes; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; C037689:benzamide; D004247:DNA