Benzo[a]pyrene diol epoxide I modification of DNA in human skin xenografts.

Human skin xenografts were established on the subscapular area of skin of nude (nu/nu NIH-Swiss background) mice. When treated with benzo[a]pyrene diol epoxide I (BPDE I), specific carcinogen-DNA adducts were formed. Separation and identification of these adducts by the 32P-postlabeling technique indicated that the 7R- and 7S-BPDE I-dpGp adducts were the major adducts. Xenografts pretreated with either allantoin or anthralin showed an increase in the major 7R- and 7S-BPDE I adducts compared to only BPDE I treatment. Likewise, we observed an increase in the quantity of different minor adducts. The ratios between the minor and major adducts in the pretreated grafts remained consistent with the ratio in the grafts treated with BPDE I only. We conclude that these modulators induce cells in the xenograft to enter S phase of the cell cycle. Moreover, we observed that these compounds altered the quantity of the minor carcinogen-DNA adducts without altering the overall ratios between the major 7R- and 7S-BPDE I-dpGp adducts and the minor carcinogen-DNA adducts.