Modifications in the carcinogen-metabolizing capacity of mouse liver treated with N-nitroso compounds.
One tenth of the LD50 as a single dose of various N-nitroso compounds (N-nitrosodimethylamine; NDMA, N-nitrosodiethylamine; NDEA, N-nitrosoethylpropylamine; NEPA, N-nitrosodipropylamine; NDPA, N-nitrosomethylethylamine; NMEA, N-nitroso-methylbutylamine; NMBA and N-nitrosoethylbutylamine; NEBA) was administrated into male mice. This dose markedly increased the hepatic contents of cytochrome P450 and cytochrome b5 and activities of NADPH-cytochrome c reductase and aryl hydrocarbon hydroxylase (AHH). The highest increase in the activity of cytochrome P450 (+142% relative to the control value) was shown in animals treated with either N-nitrosoethylpropylamine or N-nitrosodiethylamine. On the other hand, the lowest increase in the activity (+16%) was revealed in animals treated with N-nitrosodimethylamine (not significant compared to the control value). Cytochrome b5 content was increased by 190% of the control value in mice treated with N-nitrosomethylbutylamine, while N-nitrosodibutylamine induced the lowest increase (+20%). The maximum increase (+182%) in the activity of aryl hydrocarbon hydroxylase was shown in animals which received N-nitrosomethylbutylamine, while the lowest increase (+23%) in animals which received N-nitrosodiethylamine. The activity of hepatic AHH was also increased above the control value in animals treated with NDMA, NEBA NDPA, NMEA and NDBA by 138, 98, 90, 89 and 69%, respectively. Identically, NADPH-cytochrome c reductase activity was increased in animals which received NEPA, NMBA, NDMA, NMEA, NDPA, NEBA and NDEA by 202, 150, 110, 95, 94, 77 and 37%, respectively.
Habib
S L
SL
Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt.
Badawi
A F
AF
Aweny
H A
HA
Mostafa
M H
MH
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism / Q000493:pharmacokinetics*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015786:Cytochromes b5 / Q000378:metabolism; D008658:Inactivation, Metabolic; D007928:Lethal Dose 50; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008861:Microsomes / Q000187:drug effects; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009603:Nitroso Compounds / Q000378:metabolism / Q000493:pharmacokinetics*
D002273:Carcinogens; D009603:Nitroso Compounds; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D009251:NADPH-Ferrihemoprotein Reductase