T. Slaga, G. Gleason, G. Mills
Jun 1, 1980
Citations
1
Influential Citations
58
Citations
Quality indicators
Journal
Cancer research
Abstract
The abilities of dihydrodiols and diol-epoxides of dibenz( a,h )anthracene, dibenz( a,c )anthracene, chrysene, 7-methylbenz( a )anthracene, and benzo( e )pyrene to initiate skin tumors in mice were determined by using a two-stage system of tumorigenesis. (±)- trans -3,4-Dihydroxy-3,4-dihydro-7-methylbenz( a )anthracene and (±)- trans -1,2-dihydroxy-1,2-dihydrochrysene were found to be more active than their corresponding parent hydrocarbons when applied topically to Sencar mice, followed by twice-weekly applications of 12- O -tetradecanoylphorbol-13-acetate. Although, (±)- trans -9,10-dihydroxy-9,10-dihydro-benzo( e )pyrene had more activity than benzo( e )pyrene, it was not significantly higher. (±)- trans -3,4-Dihydroxy-3,4-di-hydrodibenz( a,h )anthracene was found to have one-half of the tumor-initiating ability of dibenz( a,h )anthracene. (±)- trans -3,4-Dihydroxy-3,4-dihydrochrysene and (±)- trans -10,11-dihydroxy-10,11-dihydrodibenz( a,c )anthracene were essentially inactive as skin tumor initiators. trans -9,10-Dihydroxy- anti -11,12-epoxy-9,10,11,12-tetrahydrobenz( e )pyrene, trans-3,4-dihydroxy-anti-1,2-epoxy-1,2,3,4-tetrahydrodibenz( a,h )anthracene, trans -10,11-dihydroxy- anti -12,13-epoxy-10,11,12,13-tetrahydrodibenz( a,c )anthracene, and trans -3,4-dihydroxy- anti -1,2-epoxy-1,2,3,4-tetrahydro-7-methylbenz( a )anthracene were also found to be inactive as tumor initiators. trans -1,2-Dihydroxy- anti -3,4-epoxy-1,2,3,4-tetrahydrochrysene had 25% of the activity of chrysene. Results show that the dihydrodiols of 7-methylbenz( a )anthracene, dibenz( a,h )anthracene, and chrysene, which are the immediate metabolic precursors of bay-region diol-epoxides, have moderate to high initiating activity, whereas the dihydrodiol of benz( e )pyrene (an extremely weak initiator) has weak activity. The bay-region diol-epoxide of chrysene was the only diolepoxide tested that had significant activity when compared to the corresponding parent hydrocarbon. Some of the dihydrodiol data provide further support for the bay-region theory of polycyclic hydrocarbon carcinogenesis.