Carcinogenicity and mutagenicity of some alkoxy cyclopenta[a]phenanthren-17-ones; effect of obstructing the bay region.

Six 11-O-alkoxy derivatives of the phenol 15,16-dihydro-11-hydroxycyclopenta[a]phenanthren-17-one were prepared and tested for their ability to initiate skin tumours on mouse skin after topical application, followed by promotion with croton oil. The 11-methoxy derivative was the most active, but was less so than the strong carcinogen 15,16-dihydro-11-methyl-cyclopenta[a]phenanthren-17-one (Ib). The 11-ethoxy derivative was somewhat less active as a tumour initiator than the 11-methoxy compound, and the 11-n-propoxy and 11-n-pentoxy derivatives were inactive. The 11-iso-propoxy and, surprisingly, the 11-n-butoxy compound possessed weak initiating activity. The phenol, which is too insoluble inorganic solvents to be tested in this way, proved to be about half as active as a skin tumour initiator compared with the 11-methyl derivative (Ib) when these compounds were injected s.c. in oil, and this was followed by topical promotion of dorsal skin remote from the site of injection. 15,16-Dihydro-15-methoxy-cyclopenta[a]phenanthren-17-one essentially lacked tumour initiating activity on mouse skin, but its 11-methyl homologue was moderately active. The carcinogenicity of the 11-alkoxy compounds was in general paralleled by their mutagenicity to Salmonella typhimurium TA100 in the Ames' test, with the exception of the 11-phenol which was not a mutagen under these conditions (plate assay).