Genotoxicity of nicotine and cotinine in the bacterial luminescence test.

Cotinine was positive in the absence of S9 in the bacterial luminescence 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 teratogenicity. In the presence of S9, cotinine was positive at 1.25 mg/ml after 9 incubation hours. In contrast, nicotine was not at any concentration or incubation time. Nicotine/cotinine mixtures were still positive at physiological concentrations, with potentiation relative to cotinine alone with and without S9. Standard additions of nicotine to other positive controls such as 2-aminoanthracene (2AA) (a mutagen causing point mutations on activation), phenol (a DNA intercalator), and N-methyl-N'-nitrosoguanidine (MNNG) (a direct-acting point mutagen) revealed a complex nicotine effect. Nicotine antagonized MNNG without S9, and potentiated MNNG with S9, 2AA with and without S9, and phenol without S9. Cotinine was not a very potent agent relative to the positive controls. Since cotinine has been considered an inactive biological monitoring 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 than thought hitherto.