Relationships between carcinogenesis in vivo and alkylation and solvolysis in vitro.
Carcinogenic bromomethyl- and chloromethylanthracenes and benz(a)anthracenes were found to react rapidly in vitro with DNA under physiological conditions and to varying degrees with nucleotides and nucleosides. The compounds were assayed for production of lung adenomas in strain A mice and relative carcinogenic potencies were compared with in vitro alkylation and with in vitro solvolysis rates. Success at quantitative correlation with carcinogenic potency was not obtained with either in vitro parameter. However, comparable noncarcinogenic compounds lacked their marked in vitro reactivity with DNA. Some potential polynuclear electrophiles, including chloromethyl derivatives of acridine and benz(c)acridine, a hydroxymethyl and an acetoxymethyl derivative of benz(a)anthracene, an acetoxymethylanthracene, and an acridinylglycine ester, were found not to be carcinogenic in the lung adenoma test.
D000236:Adenoma / Q000139:chemically induced; D000477:Alkylating Agents; D000818:Animals; D002273:Carcinogens; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA; D005260:Female; D008175:Lung Neoplasms / Q000139:chemically induced; D051379:Mice; D013329:Structure-Activity Relationship
D000477:Alkylating Agents; D002273:Carcinogens; D004247:DNA