M. Coombs, T. Bhatt, C. Croft
Apr 1, 1973
Citations
0
Influential Citations
57
Citations
Quality indicators
Journal
Cancer research
Abstract
The relationship between structure and carcinogenicity in fifteen new cyclopenta[a]phenanthrene derivatives, all closely related to the potent carcinogen [15,16-dihydro-11-methyl-cyclopenta[a]phenanthren-17-one (compound VI)], was tested by mouse skin painting. Each mouse received 30 µg of the compound on the dorsal skin twice weekly for 1 year, and the experiment was concluded at the end of the 2nd year. Nine compounds were active carcinogens. The chrysene analog (1,2,3,4-tetrahydro-11-methylchrysen-1-one) displayed the same high potency as did the ketone (VI), while the parent, unsubstituted chrysene was inactive. The 11-methyl-17-ol derived from compound VI and the 11-methoxy-7-methyl-17-ketone also possessed marked activity. The 7-methyl-17-ketone was much less active than VI while the 2-, 3-, 4-, and 6-methyl isomers and the 11,12-dihydro derivative were inactive. The 11-ethyl homolog was also much less active than VI and the 11- n -butyl homolog was almost without activity. The positional isomer 15,16-dihydro-11-methyl-cyclopenta[a]phenanthren-15-one was only weakly active, but moderate carcinogenicity was associated with the 6-methoxy and 16-hydroxy derivates of VI. The results are discussed in connection with the possible mode of action of these compounds and in relation to hypothetical routes of steroid degradation, especially by anaerobic gut bacteria.