MUTAGENICITY TESTING OF 9-N-SUBSTITUTED ADENINES AND THEIR N-OXIDATION PRODUCTS

Adenine together with certain 9-N-substituted derivatives such as 9-me thyl, 9-benzyl, 9-benzhydryl, and 9-trityl were tested against Salmone lla typhimurium strains TA97, TA98, and TA100 in the absence and prese nce of rat hepatic S9 prepared from Aroclor 1254 pretreated rats. All compounds were positive toward TA98 in the presence of the metabolic a ctivating system, whereas they all lacked mutagenic activity in the ab sence of S9, and toward TA97 and TA100 with or without S9 when tested at 100 ng/plate. A similar pattern was observed for the corresponding 1-N-oxides. 6-Hydroxylaminopurine was not mutagenic toward TA100 at 10 0 ng/plate, whereas it was toxic toward TA97 and TA98 at this level. W hen tested at 1 ng/plate, hydroxylaminopurine was still toxic to TA98 but produced twice the spontaneous reversion rate to TA97 without meta bolic activation. Surprisingly, 9-methyl-6-hydroxylaminopurine was onl y active toward TA98 in the presence of S9, whereas 9-benzyl-6-hydroxy laminopurine was highly active toward TA97 and T100 in the absence of S9 and even more active in the presence of S9. This compound was inact ive toward TA98 in the absence of S9. The results generally support th e concept that nuclear N-oxidation of aminoazaheterocycles is a detoxi cation process, whereas N-hydroxylation of the exo amino group is a to xication reaction.