Similarities in the formation and removal of covalent DNA adducts in benzo(a)pyrene-treated BALB/3T3 variant cells with different induced transformation frequencies

Abstract

Classes of cell variants isolated from BALB/3T3-A31 clone 1 showing high, intermediate, and low susceptibility to ultraviolet light-induced transformation also demonstrated a differential response to benzo(a)pyrene (BP)-induced transformation. On the other hand, these variants showed an identical susceptibility to the killing effect of these carcinogens. The extent of BP binding to DNA was found to be very similar in all three classes of variants under transforming conditions. BP:DNA adducts from the variant cells were analyzed by high-pressure liquid chromatography. The same adducts (N2-(10S-[7R,8S,9R-trihydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene]yl)deoxyguanosine and a minute amount of the 7S enantiomer) were detected in the highly susceptible, the intermediately susceptible, and the resistant variant clones. Removal of the BP:DNA adduct occurred at an equally slow rate in all three classes of variant cells. These results indicate that the formation of stable covalent DNA adducts is not a sufficient condition for induction of transformation. Processes other than formation and removal of the stably bound BP:DNA covalent adducts are thus major factors controlling the susceptibility of BALB/3T3-A31 clone 1 variant cells to BP-induced transformation.