COMPARISON OF 7,12-DIMETHYLBENZ(A)ANTHRACENE-DNA ADDUCTION IN THE EPIDERMIS OF 2 LINES OF MICE SELECTED FOR RESISTANCE (CAR-R) OR SUSCEPTIBILITY (CAR-S) TO SKIN CARCINOGENESIS

Two lines of mice were produced by bidirectional selective breeding: o ne resistant (CAR-R) and one susceptible (CAR-S) to two-stage skin car cinogenesis by dimethylbenz(a)anthracene and 12-O-tetradecanoylphorbol -13-acetate. The dimethylbenz(a)anthracene-DNA adduct formation was co mpared in the two lines by a postlabeling procedure so as to determine whether the striking interline difference observed as to tumor incide nce could (in part) be due to differences in the formation of DNA-reac tive metabolites. Results show that qualitatively, adduct profiles in CAR-R and CAR-S epidermis are similar. Quantitatively, the total bindi ng level is slightly higher in CAR-S versus CAR-R mice during the 30-d ay follow-up. However, these minor differences do not increase in func tion of the response to selection observed through three consecutive g enerations. A 2- or 4-week promotion with 12-O-tetradecanoylphorbol-13 -acetate enhances the decrease of adduct level in the two lines. This effect is somewhat more pronounced in CAR-S mice. Results strongly sug gest that the expression of the genes responsible for CAR-R/CAR-S phen otypic difference affects mainly the postinitiation stages.