Benzo[a]pyrene diol epoxide DNA adduct formation in transformable and non-transformable human foreskin fibroblast cells in vitro.

Abstract

The uptake of benzo[a]pyrene (BP) by low passage (LP) and high passage (HP) human skin fibroblast cells is followed by its transport into the nucleus as the parent compound. When the LP and HP cells were treated with BP for 24 h and the DNA was isolated and enzymatically digested, several DNA adducts were detected. In both the LP and HP cells a small amount of the radiolabel was associated with the 7 beta-BPDE-I-dG, 7 alpha-BPDE-I-dG and BPDE-II-dG adducts. Although there were no major qualitative differences in the adducts formed in the LP and HP cells, a higher proportion of the radiolabel was associated with the 7 beta-BPDE-I-dG adduct in the LP cells. When LP or HP cells were treated with BPDE-I, the ultimate carcinogenic form of BP, similar levels of DNA modification were observed in the two cell types and the h.p.l.c. profiles of these adducts were essentially identical. BPDE-I induced a carcinogenic event in the LP but not the HP cells as measured by anchorage independent growth in soft agar and cellular invasiveness of the chick embryonic skin organ cultures.