Metabolism of 4-(methyhiitrosamino)-l-(3-pyridyi)-1-butanone (NNK) a tobacco-specific carcinogen, by rabbit nasal microsomes and cytochrome P450s NMa and NMb

Abstract

The publishers would like to apologise for mis-printing the last paragraph to the Introduction of die above paper. The corrected paragraph follows:. Recently two novel forms of P450 (P450NMa and -NMb) have been purified from rabbit nasal microsomes (6). The purified P450NMa and -NMb have monomeric mol. wts of 49.5 and 51 kDa respectively. In the ferric form NMa is in the low-spin state, whereas NMb is predominandy in the high-spin state (6). P450NMa exhibits high activity toward a number of xenobiotics, including hexamethylphosphoramide, phenacetin, Nnitrosodiethylamine and ethanol, with turnover numbers that are the highest or among the highest seen with all rabbit P450s examined. P450NMb displays high activity toward an endogenous substrate, testosterone (7). More recent studies indicate that NMb is also active in die metabolism of progesterone and estradiol (7). In the present work, in addition to the studies on NNK metabolism by rabbit olfactory and respiratory microsomes, the roles of P450NMa and -NMb in the metabolism of NNK were determined in a reconstituted system. The effects of nicotine and DAS on NMa-catalyzed NNK metabolism were also investigated. © 1993 Oxford University Press.