GENOTOXICITY OF NICOTINE AND COTININE IN THE BACTERIAL LUMINESCENCE TEST

Cotinine was positive in the absence of S9 in the bacterial luminescen ce genotoxicity test at 1.25 mg/ml (9-15 h incubation) and at 2.50 mg/ ml (18-30 incubation hours) signifying potential mutagenicity and tera togenicity. In the presence of S9, cotinine was positive at 1.25 mg/ml after 9 incubation hours. In contrast, nicotine was not at any concen tration or incubation time. Nicotine/cotinine mixtures were still posi tive at physiological concentrations, with potentiation relative to co tinine alone with and without S9. Standard additions of nicotine to ot her positive controls such as 2-aminoanthracene (2AA) (a mutagen causi ng point mutations on activation), phenol (a DNA intercalator), and N- methyl-N'-nitrosoguanidine (MNNG) (a direct-acting point mutagen) reve aled a complex nicotine effect. Nicotine antagonized MNNG without S9, and potentiated MNNG with S9, 2AA with and without S9, and phenol with out S9. Cotinine was not a very potent agent relative to the positive controls. Since cotinine has been considered an inactive biological mo nitoring marker of nicotine absorption in humans, the present results indicate that the many health effect correlations based on cotinine in urine, serum, saliva, and blood may involve more cause and effect tha n thought hitherto.