Effects of mutagenic and non-mutagenic aniline derivatives on rat liver drug-metabolizing enzymes.
1. The effect of 4,4'-methylene bis(2-chloroaniline) (MOCA), 4,4'-methylene dianiline (MDA) and 4,4'-sulphonyldianiline (Dapsone) in vivo on xenobiotic biotransformation in male rat liver was studied. 2. Treatment with MOCA or MDA but not Dapsone caused a dose-dependent increase in ethoxyresorufin O-deethylase activity and a concomitant decrease in aldrin epoxidase activity in male rats. 3. Treatment with MOCA or MDA resulted in dose-dependent increases in ethoxycoumarin O-deethylation and epoxide hydrolation, while only MOCA induced cytosolic glutathione S-transferase activity. 4. Treatment with Dapsone resulted in no changes in xenobiotic biotransformation except for the induction of aniline hydroxylation. 5. The results are consistent with the contention that there is a relationship between carcinogenic chemicals and particular alterations in the activities of biotransformation enzymes.
Wu
K
K
National Institute of Occupational Health and Safety, University of Sydney, NSW, Australia.
Leslie
C L
CL
Stacey
N H
NH
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000814:Aniline Compounds / Q000494:pharmacology*; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001711:Biotransformation; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003622:Dapsone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000378:metabolism; D008297:Male; D008753:Methylenebis(chloroaniline) / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009153:Mutagens; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000814:Aniline Compounds; D001559:Benzhydryl Compounds; D009153:Mutagens; D008753:Methylenebis(chloroaniline); D003622:Dapsone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; C019647:aldrin epoxidase; D015660:7-Alkoxycoumarin O-Dealkylase; D000815:Aniline Hydroxylase; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C009505:4,4'-diaminodiphenylmethane