Methylene-bridged bay region chrysene and phenanthrene derivatives and their keto-analogs: mutagenicity in Salmonella typhimurium and tumor-initiating activity on mouse skin.
A series of methylene-bridged and keto-bridged bay region derivatives of chrysene and phenanthrene were prepared and evaluated for mutagenic activity in Salmonella typhimurium TA100 and for tumor-initiating activity on CD-1 mouse skin. The compounds included in this series were 4H-cyclopenta[def]phenanthrene, 4H-cyclopenta[def]phenanthrene-4-one, 1-methyl-4H-cyclopenta[def]phenanthrene, 1-methyl-4H-cyclopenta[def] phenanthren-4-one, 4H-cyclopenta[def] chrysene, and 4H-cyclopenta[def] chrysen-4-one. Among these compounds only 4H-cyclopenta[def]phenanthrene and 1-methyl-4H-cyclopenta[def]phenanthren-4-one were not significantly mutagenic when assayed with metabolic activation using Aroclor-induced rat liver homogenate. None of the compounds assayed were active without metabolic activation. 4H-Cyclopenta[def]chrysene was the most tumorigenic of the methylene-bridged bay region PAH tested on mouse skin. At a dose of 1.0 mg this compound resulted in 100% of the animals bearing papillomas with 5.63 papillomas/animal. 4H-Cyclopenta[def]chrysen-4-one and 1-methyl-4H-cyclopenta[def]phenanthrene displayed weak tumorigenic activity at a total initiating dose of 1.0 mg.
D000818:Animals; D001711:Biotransformation; D002911:Chrysenes / Q000633:toxicity*; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000378:metabolism; D010616:Phenanthrenes / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012486:Salmonella typhimurium / Q000187:drug effects; D012878:Skin Neoplasms / Q000139:chemically induced*; D013329:Structure-Activity Relationship
D002911:Chrysenes; D009153:Mutagens; D010616:Phenanthrenes