Mutagenicity of diol-epoxides and tetrahydroepoxides of benz(a)acridine and benz(c)acridine in bacteria and in mammalian cells

• Published in: Cancer research (Chicago, Ill.) Ill.), 1983-04, Vol.43 (4), p.1656-1662
• Main Authors: Wood, A W, Chang, R L, Levin, W, Ryan, D E, Thomas, P E, Lehr, R E, Kumar, S, Schaefer-Ridder, M, Engelhardt, U, Yagi, H, Jerina, D M, Conney, A H
• Format: Article
• Language: English
• Subjects: Acridines - toxicity; Animals; Biotransformation; Cell Line; Cell Survival - drug effects; Cricetinae; Cricetulus; Epoxy Compounds; Kidney; Male; Microsomes, Liver - metabolism; Mutagenicity Tests; Mutagens; Mutation; Rats; Salmonella typhimurium; Salmonella typhimurium - drug effects; Structure-Activity Relationship
• ISSN: 0008-5472

The mutagenic activities of benz(a)acridine, benz(c)acridine, and a number of their derivatives, including 12 epoxides and diol-epoxides, were examined in bacterial and mammalian cells to determine the importance of bay-region activation of azapolycyclic aromatic hydrocarbons. In Salmonella typhimurium strain TA98, the diastereomeric day-region 3,4-diol-1,2-epoxides of benz(c)acridine, in which the benzylic hydroxyl group is either cis (diol-epoxide 1) or trans (diol-epoxide 2) to the epoxide oxygen, had equivalent mutagenic potency (250 to 300 His super(+) revertants/nmol), while in S. typhimurium) strain TA100, diolepoxide 1 induced 5100 His super(+) revertants/nmol and was approximately twice as active as was diol-epoxide 2. In Chinese hamster V79 cells, the diol-epoxide 2 isomer of benz(c)acridine 3,4-diol-1,2-epoxide was approximately twice as mutagenic (4.5 8-azaguanine-resistant colonies/10 super(5) surviving cells/nmol)as diol-epoxide 1. The results provide initial evidence that the bay-region theory can be extended to certain azapolycyclic aromatic hydrocarbons and indicate that the position of the nitrogen heteroatom can markedly affect mutagenic activity.