The formation of epidermal
DNA adducts from 9-fluoro-7,12-dimethylbenz(a)anthracene (9-F-DMBA) was compared with
7,12-dimethylbenz(a)anthracene (DMBA) and
10-fluoro-7,12-dimethylbenz(a)anthracene (10-F-DMBA) in SENCAR mice. 9-F-DMBA is equipotent, whereas
10-F-DMBA is more potent than DMBA for skin
tumor initiation in this mouse stock. The quantity of covalently bound
DNA adducts was essentially identical between 9-F-DMBA and DMBA at all doses tested in the range of 10 to 100 nmol/mouse. These results correlated closely with the dose-response relationships for
tumor initiation by the two
hydrocarbons. A quantitative comparison of the
hydrocarbon-
DNA adducts formed after topical application of 100 nmol of DMBA, 9-F-DMBA, and
10-F-DMBA yielded interesting results. The total binding for the three
hydrocarbons at this dose was 16.2 +/- 2.6, 18.4 +/- 2.4, and 52.3 +/- 6.8 pmol/mg of epidermal
DNA, respectively. Analysis of these
DNA adduct samples by dihydroboronate chromatography demonstrated marked reductions in the percentage of syn-diol-
epoxide-
DNA adducts with both 9-F-DMBA (24%) and
10-F-DMBA (18%) compared with DMBA (57%). Analysis of
DNA adduct samples from DMBA-, 9-F-DMBA-, and 10-F-DMBA-treated mice (100 nmol/mouse) by high-pressure liquid chromatography revealed qualitatively similar profiles. However, a quantitative comparison of the three major
DNA adducts, tentatively identified as anti-diol-
epoxide-
deoxyguanosine (Peak I), syn-diol-
epoxide-
deoxyadenosine (Peak II), and anti-diol-
epoxide-
deoxyadenosine (Peak III), revealed significant differences. With both 9-F-DMBA and
10-F-DMBA there were marked increases (236% and 644%, respectively) in the quantity of Peak I compared to DMBA. On the other hand, Peak II was formed in approximately equal amounts with DMBA and
10-F-DMBA but only 50% of the DMBA value with 9-F-DMBA. Interestingly, Peak III was formed in approximately equal amounts with both DMBA and 9-F-DMBA but was increased to 337% of the DMBA value with
10-F-DMBA. Thus, the actual level of Peak III (tentatively identified as anti-diol-
epoxide-
deoxyadenosine) correlated closely with the
tumor-initiating activity of these three
hydrocarbons, whereas the levels of the other two adducts did not. These data suggest that formation of a specific
DNA adduct may be important for DMBA skin
tumor initiation. These data are discussed in relation to skin
tumor initiation by other
hydrocarbons.