GENOTOXIC AND BIOCHEMICAL EFFECTS OF DIMETHYLAMINE

The genotoxicity of dimethylamine (DMA) was investigated in the D7 str ain of Saccharomyces cerevisiae. DMA was able to induce mitotic gene c onversion and point reverse mutation in the presence of metabolic acti vation (S9 fraction). To study the co-mutagenicity/co-carcinogenicity or toxicity of DMA, changes in xenobiotic metabolizing enzymes were st udied in purified microsomes from DMA-induced mice or rats receiving a single or three consecutive doses (25 or 50 mg/kg body wt). Pentoxyre sorufin O-dealkylase (class IIB1 P450, PROD), ethoxyresorufin O-deethy lase (IA1, EROD) and p-nitrophenol hydroxylase (IIE1, pNPH) were all a ffected by DMA treatment with a loss of activity of 62, 55 and 54% in the mouse, or 64, 25 and 56% in the rat for PROD, EROD and pNPH activi ties, respectively, at the highest tested dose. No significant alterat ion of P450 IIIA-like activity was seen. Results indicated that the me tabolites of DMA induced genetic activity in yeast. In addition, a cle ar non-specific hepatotoxic effect was recorded as a significant reduc tion in activity of the selected monooxygenases.