The carcinogenic tobacco-specif ic nitrosamines 4-(methylnitrosemino) -1-(3-pyridyl) -1-butanone (NNK) and N'-nitrosonornicotine (NNN), as well as the model compound 4-(carbethoxynitrosamino) -1-(3-pyridyl) -1butanone, were synthesized with tritium at the 5-position of the pyridine ring. In each case, the tritium labelled compound was prepared by catalytic tritium replacement of the corresponding brominated precursor. This intermediate as well as the a-hydroxy compounds , 1 and 2 are unstable and have not been synthesized. However, 4-(carbethoxynitrosamino) -1-(3-pyridyl) -1-butanone, 1, is a stable precursor to A (2.3). In order to investigate the interactions of NNK, NNN, and 1 with DNA and protein, the tritium labelled compounds were required. Metabolic studies of "K and "N indicate that hydroxylation of the pyridine ring is not a major process ( 4 ) . Thus, to avoid exchange L n -0, tritium was specifically incorporated at the 5-position of the pyridine ring. DNA and globln adducts Scheme 1 RESULTS AND DISCUSSION The synthesis of [5-3H]NNK is illustrated in Scheme 2. The method is based on that used for unlabelled "K ( 5 , 6 ) . Ethyl 5bromonicotinate, 2, was reacted with N-methylpyrrolidinone, 5 , to give the intermediate condensation product 2. Tritiation of 1 by J. C. Wiley Jr. et al.