Comparative gastrointestinal enzyme activity and activation of the promutagen 2,6-dinitrotoluene in male CD-1 mice and male Fischer 344 rats.
Comparative intestinal nitroreductase, azo reductase, beta-glucuronidase, dechlorinase and dehydrochlorinase activities in young male Fischer 344 rats and young male CD-1 mice were measured in vitro while the comparative biotransformation of 2,6-dinitrotoluene to mutagenic metabolites was determined in vivo. The mice, which exhibit a high spontaneous incidence of hepatomas, had markedly greater nitroreductase activity and metabolized significantly more 2,6-dinitrotoluene to mutagenic metabolites than did Fischer 344 rats, which show a low incidence of liver tumors. Results of this study indicate that species differences in the incidence of hepatomas may be influenced by microbial flora and/or the biotransformation of xenobiotics in the G.I. tract.
Chadwick
R W
RW
Health Effects Research Laboratory Environmental Research Center, U.S. Environmental Protection Agency Research, Triangle Park, N.C. 27711.
George
S E
SE
Chang
J
J
Kohan
M J
MJ
Dekker
J P
JP
Long
J E
JE
Duffy
M C
MC
D000818:Animals; D001711:Biotransformation; D004136:Dinitrobenzenes / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism; D007422:Intestines / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008190:Lyases / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009578:Nitrobenzenes / Q000378:metabolism*; D009601:Nitroreductases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D004136:Dinitrobenzenes; D009578:Nitrobenzenes; D009601:Nitroreductases; D005966:Glucuronidase; D008190:Lyases; C023514:2,6-dinitrotoluene