Investigations on benzyltoluenes. I. Induction of microsomal cytochrome P-450 and UDP-glucuronosyltransferase by tetrachlorobenzyltoluenes and by the condensate.
Tetrachlorobenzyltoluene (TCBT) (Ugilec 141) was investigated in induction experiments in male and female Wistar rats with long-term (50, 100 and 300 mg/kg p.o. daily for 28 days) and short-term administration (300 mg/kg once and 100 mg/kg daily for 4 days). The increase in total cytochrome P-450 did not exceed the factor of 1.9 compared to controls, while benzphetamine N-demethylase rose up to 3.5-fold the levels measured in controls, with very low induction of benzo(a)pyrene hydroxylase or ethoxyresorufin O-deethylase. Parallel investigations of UDP-glucuronosyltransferase showed induction of testosterone glucuronidation (1.7-fold). Administration (300 mg/kg body wt. once) of a pyrolysate of TCBT resulted in a marked increase in cytochrome P-450c dependent reactions (benzo(a)pyrene hydroxylase, ethoxyresorufin O-deethylase).
von Meyerinck
L
L
Abteilung Pharmakologie für Pharmazeuten, Universitäts-Krankenhaus Eppendorf, F.R.G.
Hufnagel
B
B
Schmoldt
A
A
Benthe
H F
HF
D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000378:metabolism
D001559:Benzhydryl Compounds; D005965:Glucuronates; C063736:Ugilec 141; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D001579:Benzopyrene Hydroxylase; D019363:Cytochrome P-450 CYP1A1; C019781:benzphetamine N-demethylase; D010089:Oxidoreductases, N-Demethylating; D014453:Glucuronosyltransferase