Genotoxic and biochemical effects of dimethylamine.
The genotoxicity of dimethylamine (DMA) was investigated in the D7 strain of Saccharomyces cerevisiae. DMA was able to induce mitotic gene conversion and point reverse mutation in the presence of metabolic activation (S9 fraction). To study the co-mutagenicity/co-carcinogenicity or toxicity of DMA, changes in xenobiotic metabolizing enzymes were studied in purified microsomes from DMA-induced mice or rats receiving a single or three consecutive doses (25 or 50 mg/kg body wt). Pentoxyresorufin O-dealkylase (class IIB1 P450, PROD), ethoxyresorufin O-deethylase (IA1, EROD) and p-nitrophenol hydroxylase (IIE1, pNPH) were all affected 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 activities, respectively, at the highest tested dose. No significant alteration of P450 IIIA-like activity was seen. Results indicated that the metabolites of DMA induced genetic activity in yeast. In addition, a clear non-specific hepatotoxic effect was recorded as a significant reduction in activity of the selected monooxygenases.
Galli
A
A
Istituto di Mutagenesi e Differenziamento CNR, Pisa, Italy.
Paolini
M
M
Lattanzi
G
G
Cantelli-Forti
G
G
Bronzetti
G
G
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001711:Biotransformation; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D019392:Cytochrome P-450 CYP2E1; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004123:Dimethylamines / Q000378:metabolism / Q000633:toxicity*; D005785:Gene Conversion / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D010088:Oxidoreductases / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D017354:Point Mutation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics
D004123:Dimethylamines; D009153:Mutagens; D003577:Cytochrome P-450 Enzyme System; C034516:dimethylamine; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating