S. Amin et al., TUMOR-INITIATING ACTIVITY ON MOUSE SKIN OF BAY-REGION DIOL-EPOXIDES OF 5,6-DIMETHYLCHRYSENE AND BENZO[C]PHENANTHRENE, Carcinogenesis, 14(10), 1993, pp. 2033-2037
Previous metabolism and DNA-binding studies indicated that 5,6-dimethy
lchrysene (5,6-diMeC) is metabolically activated in mouse skin through
formation of its 1,2-dihydrodiol (5,6-diMeC-1,2-diol) and bay region
diol-epoxide (anti-5,6-diMeC-1,2-diol-3,4-epoxide). These metabolites
were tested as tumor initiators on mouse skin. Included for comparison
were syn-5,6-diMeC-1,2-diol-3,4-epoxide and y-2,1-epoxy-4,3,2,1-tetra
hydrobenzo[c]phenanthrene (anti-B[c]Ph-4,3-diol-2,1-epoxide). At an in
itiating dose of 100 nmol/mouse, 5,6-diMeC-1,2-diol and anti-5,6-diMeC
-1,2-diol-3,4-epoxide were significantly more tumorigenic than 5,6-diM
eC, inducing 7.1 and 3.9 skin tumors per mouse respectively compared t
o 1.1 induced by 5,6-diMeC. Similar results were obtained at an initia
ting dose of 33 nmol/mouse. This is the first example of a methylated
polynuclear aromatic hydrocarbon bay region diol-epoxide which is more
tumorigenic than its parent hydrocarbon on mouse skin. syn-5,6-diMeC-
1,2-diol-3,4-epoxide was only weakly tumorigenic. Comparisons of anti-
5,6-diMeC-1,2-diol-3,4-epoxide and anti-B[c]Ph-4,3-diol-2,1-epoxide de
monstrated that the latter was a stronger tumor initiator. The results
of this study confirm the bay region diol-epoxide metabolic activatio
n pathway of 5,6-diMeC but do not provide an explanation for the relat
ively weak tumorigenicity of this hydrocarbon on mouse skin.