Mutagenicity of bay-region amino-substituted cyclopenta[a]phenanthrenes and 2- and 5-aminochrysene.
The relative mutagenic potentials of 11-amino-16,17-dihydro-15H-cyclopenta[a]phenanthrene, its 17-keto derivative, and 2- and 5-aminochrysene have been compared in Salmonella typhimurium TA98 and TA100 in the presence of a postmitochondrial liver preparation from Aroclor 1254 induced rats. The 11-amino hydrocarbon is a very weak mutagen (0.27 revertants/nmol), whereas the 11-amino-17-ketone is much more active (129 revertants/nmol). 2-Aminochrysene is the most mutagenic arylamine ( approximately 500 revertants/nmol) among these compounds, but its 5-amino isomer is much less active (0.9 revertants/nmol). Possible reasons for these marked differences are suggested. Use of TA98 with over-expressing O-acetyltransferase (YG 1024) and deficient in this enzyme (TA98/l,8-DNP(6)) with the 11-amino-17-ketone and with 5-aminochrysene clearly indicates the importance of this enzyme in their bioactivation, implying oxidation of the amino group to the hydroxylamine in both these compounds.
Catterall
F S
FS
Molecular Toxicology Group, School of Biological Sciences, University of Surrey, Guildford, GU2 7XH, Surrey, UK.
Coombs
M M
MM
Ioannides
C
C
Sepiol
J J
JJ
Wilson
J
J
D000736:Androstenes / Q000633:toxicity*; D000818:Animals; D018383:Bay-Region, Polycyclic Aromatic Hydrocarbon; D002911:Chrysenes / Q000633:toxicity*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship
C431584:11-amino-16,17-dihydro-15H-cyclopenta(a)phenanthrene; D000736:Androstenes; D002911:Chrysenes; D009153:Mutagens; C100101:6-chrysenamine; C431550:2-aminochrysene