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Enzymic Lesions of Nicotinamide Adenine Dinucleotide Biosynthesis in Hepatomas and in Azo Dye Carcinogenesis¹

Oklahoma State University, Agricultural Experiment Station, Department of Biochemistry, Stillwater, Oklahoma 74075

Several enzymes involved in nicotinamide adenine dinucleotide (NAD) biosynthesis were assayed in transplanted and azodye-induced primary hepatomas in order to determine the enzymic lesion responsible for the low level of NAD present in these tumors. The same enzymes were also investigated in precancerous livers of 3'-methyl-4-dimethylaminobenzene (3'-Me-DAB) fed rats and in rats receiving 3'-Me-DAB and 4'-Me-DAB i.p., as well as rats fed -naphthyl isothiocyanate. It was concluded that the low level of NAD in the tumors examined was probably due to the deletion of enzymes in the tryptophan-to-NAD pathway and to decrease in activity of nicotinic acid mononucleotide pyrophosphorylase which catalyzes the rate-limiting step in the nicotinamide-to-NAD pathway. Changes in these enzymes in precancerous liver did not satisfy Reid's criteria for key steps in the carcinogenic process.

¹ Supported in part by Grant No. GM-10066 from the NIH and by Grants No. GM-1659 and GB-4695 from the National Science Foundati on. A preliminary report of a portion of this work has been published (46).

² Present address, Department of Medical Chemistry, Osaka Medical College, Osaka, Japan.

³ Reprint requests should be addressed to this author.

Received 7/ 5/66. Accepted 11/ 3/66.