Methylglyoxal: genotoxicity studies and its effect in vivo on the hepatic microsomal mono-oxygenase system of the mouse.
The genotoxic potential of methylglyoxal (MG) was studied in Saccharomyces cerevisiae D7 and in Salmonella typhimurium TA97 and TA102 in the presence and in the absence of metabolic activation system (S9 fraction) prepared from mouse liver induced with beta-naphthoflavone (beta-NF) and sodium phenobarbital (PB). The in vivo effects on the hepatic microsomal mixed function mono-oxygenase system induced by MG were studied in untreated, beta-NF or PB pre-treated mice. MG was a direct-acting mutagen in S. typhimurium TA97 and TA102 when tested up to a maximum concentration of 0.47 mg/plate. Mitotic gene conversion was also induced by MG in the yeast S. cerevisiae D7. A weak but significant effect on reverse point mutation was also found in S. cerevisiae. Genetic activity was lower in the presence of S9 fraction in yeast test. In the in vivo studies, MG (at the total dose of 600 mg/kg) was shown to increase the aminopyrine N-demethylase (APD) and p-nitroanisole O-demethylase (p-NAD) activities in uninduced mice. Cytochrome P-450 content (cyt P-450) and ethoxycoumarin O-deethylase activity (ECD) were also weakly enhanced by MG treatment. In contrast, no significant changes in mono-oxygenase activities were seen in beta-NF- or PB-treated mice after MG injection.
Bronzetti
G
G
Istituto di Mutagenesi e Differenziamento, CNR, Pisa, Italy.
Corsi
C
C
Del Chiaro
D
D
Boccardo
P
P
Vellosi
R
R
Rossi
F
F
Paolini
M
M
Cantelli Forti
G
G
D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D011765:Pyruvaldehyde / Q000633:toxicity*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics; D012486:Salmonella typhimurium / Q000187:drug effects
D000447:Aldehydes; D009153:Mutagens; D011765:Pyruvaldehyde; D006899:Mixed Function Oxygenases