S-oxygenation of thiobencarb (Bolero) in hepatic preparations from striped bass (Morone saxatilis) and mammalian systems.
The in vitro S-oxygenation of thiobencarb (Bolero; p-chlorobenzyl N,N-diethylthiocarbamate) in the presence of hepatic microsomes from freshwater- and seawater-adapted striped bass was investigated. Thiobencarb S-oxide was the principal metabolite and accounted for 98% of the total thiobencarb metabolized by striped bass liver microsomes. Studies on the biochemical mechanisms for striped bass hepatic S-oxygenation suggest that this reaction is catalyzed largely by the flavin-containing monooxygenase and to a lesser extent by cytochromes P-450. Following the short incubation period used, no thiobencarb sulfone was detected and no evidence was found for a contribution of cooxidation in the S-oxidation of thiobencarb. This conclusion was supported by studies with microsomes and purified mammalian monooxygenases which also metabolized thiobencarb without cooxidizing factors. Highly purified cytochrome P-450IIB-1 S-oxygenated thiobencarb more efficiently than highly purified hog liver flavin-containing monoxygenase. Thiobencarb S-oxide and thiobencarb sulfone were efficient carbamylating agents and reacted with thiol and amine nucleophiles, whereas thiobencarb itself was relatively stable to transthiocarbamylation. Monooxygenase-catalyzed S-oxygenation of thiobencarb by striped bass liver microsomes may represent a bioactivation process which could explain the known toxicity of thiobencarb in fish.
Cashman
J R
JR
Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, California 94143-0446.
Olsen
L D
LD
Nishioka
R S
RS
Gray
E S
ES
Bern
H A
HA
D000818:Animals; D001492:Bass / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000494:pharmacology; D007306:Insecticides / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000494:pharmacology; D051381:Rats; D013450:Sulfones / Q000378:metabolism; D013552:Swine; D013859:Thiocarbamates / Q000378:metabolism*
D007306:Insecticides; D013450:Sulfones; D013859:Thiocarbamates; D003577:Cytochrome P-450 Enzyme System; C037925:benthiocarb; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)