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Mechanisms of Inhibition by Ascorbate of Microbial Mutagenesis Induced by N-Nitroso Compounds¹

Department of Biochemistry, New York University Dental Center, New York, New York 10010

Mutagenesis induced by N-methyl-N-nitrosoguanidine (MNNG) and dimethylnitrosamine (DMN) in Salmonella TA 1530 was inhibited by ascorbate. Inhibition of MNNG-induced mutagenesis resulted from a reaction between ascorbate and MNNG that led to consumption of MNNG. The rate of this reaction was considerably enhanced by catalytic amounts of Cu(II) and Fe(III). No direct reaction between DMN and ascorbate was detectable, but relatively high concentrations of Cu(II) enhanced inhibition of DMN-induced mutagenesis by ascorbate. Added protein reduced the effectiveness of Cu(II) as a catalyst of the reaction between ascorbate and MNNG, which suggested that the microsomal protein necessary to activate DMN, may reduce the concentration of free Cu(II) and thereby lower its catalytic efficiency. Mutagenesis by N-methyl-N-nitrosourea was not inhibited by ascorbate.

¹ Presented in part at the Ninth Annual Meeting of the Environmental Mutagen Society, San Francisco, Calif., March 9 to 13, 1977. Supported by USPHS Research Grant CA-19023.

Received 1/26/78. Accepted 4/ 4/78.