Differences in cytochrome P450-mediated biotransformation of 1,2-dichlorobenzene by rat and man: implications for human risk assessment

Chemical Research in Toxicology
A M HissinkP J Van Bladeren

Abstract

The oxidative biotransformation of 1,2-dichlorobenzene (1,2-DCB) was investigated using hepatic microsomes from male Wistar, Fischer-344 and Sprague-Dawley (SD) rats, phenobarbital (PB)- and isoniazid (ISO) pretreated male Wistar rats and from man. In addition, microsomes from cell lines selectively expressing one cytochrome P450 (P4502E1, 1A1, 1A2, 2B6, 2C9, 2D6, /A6 and 3A4) were used. The rate of conversion was 0.09 nmol/min/mg. protein for both Wistar and Fischer-344 rat microsomes, 0.04 for SD-microsomes and 0.14 for human microsomes. Induction of Wistar rats with isoniazid (ISO, a P4502E1 inducer) or phenobarbital (PB, a P4502B1/2 inducer) resulted in an increased conversion rate of 0.20 and 0.42 nmol/min/mg. protein, respectively. Covalent binding of radioactivity to microsomal protein was similar for Wistar, Fischer and ISO-pretreated rats (16-17% of total metabolites), whereas induction with PB resulted in an increased covalent binding of 23% of total metabolites. Covalent binding was 31% for SD-microsomes and only 4.6% for human microsomes. Ascorbic acid notably reduced the amount of covalently bound metabolites for the SD-microsomes only, indicating that for these microsomes quinones were likely to be involved in thi...Continue Reading

References

Oct 1, 1991·Toxicology and Applied Pharmacology·C den BestenP J van Bladeren
May 1, 1988·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·N NarasimhanR P Hanzlik
Jan 1, 1996·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·A M HissinkP J Van Bladeren
Jul 1, 1997·Toxicology and Applied Pharmacology·A M HissinkP J Van Bladeren

❮ Previous
Next ❯

Citations

Apr 4, 2013·SAR and QSAR in Environmental Research·Y SakurataniM Hayashi
Sep 1, 2007·Journal of Toxicology and Environmental Health. Part a·Djohan DjohanElizabeth Christensen
May 12, 2012·American Journal of Industrial Medicine·Katarina KulhankovaPeter S Thorne
Sep 9, 2004·Chemical Reviews·Bernard MeunierSason Shaik

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antitubercular Agents (ASM)

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.

Antitubercular Agents

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.