US EPA

660035 

Journal Article 

Abstract 

Metabolism of benzene derivatives by P450IIB1 and P450IIE1 to protein- and DNA-bound products 

Gut, I; Frantík, E; Souček, P; Filipcová, B 

1992 

1 

Mutation Research
ISSN: 0027-5107
EISSN: 1873-135X 

271 

2 

172 

English 

10.1016/0165-1161(92)91221-C 

WOS:A1992HN59700139 

Inhalation exposure of male wistar rats to benzene, toluene, ethylbenzene, o-xylene, m-xylene or p-xylene resulted in markedly modified in vitro microsomal p450-catalyzed metabolism of various substrates indicating induction of p450iib1 and p450iie1. it has also been confirmed by sds-page electrophoresis revealing protein bands of corresponding molecular weights. western blotting and antibody analysis confirmed induction of these p450 forms. the induction of p450iib1 markedly increased conversion of [14c]toluene and [14c]chlorobenzene to water-soluble metabolites and correspondingly to products covalently bound to microsomal proteins and calf-thymus dna. the induction of p450iie1 resulted in a markedly increased metabolism of [14c]benzene and also [14c]aniline and there was a corresponding increase in water-soluble metabolites and metabolites bound covalently to microsomal proteins and dna. at low benzene concentrations the formation of covalently bound products was several times higher than that of soluble metabolites indicating that at in vivo relevant benzene concentrations the induction of p450iie1 could be responsible for substantially increased metabolic activation of benzene to potentially mutagenic or carcinogenic metabolites.