Effect of acrylamide monomer on hepatic CYP1A1 monooxygenase induction in rainbow trout.
1. Rainbow trout hepatic microsomes were pre-incubated in vitro with 1 pM, 1 nM, and 1 microM acrylamide for 20 or 30 min and ethoxyresorufin-O-deethylase (EROD) was measured. In vitro pre-incubation did not produce a significant decrease in EROD catalytic activity. 2. The effects of 50 ppm acrylamide monomer on hepatic CYP1A1 mRNA and CYP1A1 isozyme steady state levels in rainbow trout were determined after 6, 10, and 14 days of exposure. 3. Acrylamide monomer produced a 35% increase, 51% decrease and 140% increase in CYP1A1 mRNA at 6, 10 and 14 days, respectively, while at the same time CYP1A1 isozyme levels were decreased 12%, 67%, and 62% and EROD activity was decreased 33%, 90%, and 86%, respectively. 4. This indicates that acrylamide treatment may result in either a change in the translation of CYP1A1 mRNA or an isozyme selective inactivation of CYP1A1 resulting in loss of CYP1A1 apoprotein. 5. The effect of acrylamide treatment on hepatic CYP1A1 induction was determined using 10 or 14 day treatment with 50 ppm acrylamide monomer in a flowthrough exposure and induction with beta-naphthoflavone (beta-NF; 100 mg/kg i.p.) for 1 or 4 days. 6. Acrylamide and 1-day beta-NF had no effect on CYP1A1 mRNA levels when compared to 1-day beta-NF treatment alone, but acrylamide and 4-day beta-NF resulted in a 74% decrease in CYP1A1 mRNA compared to 4-day beta-NF treatment alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology and Toxicology Medical College of Wisconsin, Milwaukee 53226.
M L
ML
Haasch
L A
LA
Sutherland
P J
PJ
Wejksnora
J J
JJ
Lech
D020106:Acrylamide; D000178:Acrylamides / Q000494:pharmacology*; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009243:NAD / Q000494:pharmacology; D010088:Oxidoreductases / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D012474:Salmon; D014158:Transcription, Genetic / Q000187:drug effects; D019324:beta-Naphthoflavone
D000178:Acrylamides; D001571:Benzoflavones; D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D009243:NAD; D020106:Acrylamide; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1