Abstract

The aims of the propose research are to investigate the mechanism of alcohol potentiation of halogenated hydrocarbon-induced hepatotoxicity, the mechanism of destruction of cytochrome P-450 by carbon tetrachloride, the effect of hypoxia on halogenated hydrocarbon-induced toxicity, and the synergistic toxicity of halogenated hydrocarbons. These studies will be conducted in rats, and carbon tetrachloride is the major chemical to be studied. The long-range goal is to understand the biochemical mechanisms by which halogenated hydrocarbons, an important group of environmental chemicals, produce cellular damage.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES003126-04
Application #
3250266
Study Section
Toxicology Study Section (TOX)
Project Start
1982-07-01
Project End
1987-04-30
Budget Start
1985-05-01
Budget End
1986-04-30
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Rochester
Department
Type
Schools of Medicine
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627

  Publications

Aniya, Y; McLenithan, J C; Anders, M W (1988) Isozyme selective arylation of cytosolic glutathione S-transferase by [14C]bromobenzene metabolites. Biochem Pharmacol 37:251-7
Veltman, J C; Anders, M W (1987) Cytotoxicity of N,N-bis(2-chloroethyl)-N-nitrosourea in hypoxic rat hepatocytes. Cancer Res 47:5087-91
Webb, W W; Elfarra, A A; Webster, K D et al. (1987) Role for an episulfonium ion in S-(2-chloroethyl)-DL-cysteine-induced cytotoxicity and its reaction with glutathione. Biochemistry 26:3017-23
Kelner, M J; McLenithan, J C; Anders, M W (1986) Thiol stimulation of the cytochrome P-450-dependent reduction of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD). Biochem Pharmacol 35:1805-7
Aniya, Y; Anders, M W (1985) Alteration of hepatic glutathione S-transferases and release into serum after treatment with bromobenzene, carbon tetrachloride, or N-nitrosodimethylamine. Biochem Pharmacol 34:4239-44
English, J C; Anders, M W (1985) Evidence for the metabolism of N-nitrosodimethylamine and carbon tetrachloride by a common isozyme of cytochrome P-450. Drug Metab Dispos 13:449-52
Webb, W W; Anders, M W (1985) Coupling of ATP synthesis to reversal of rat liver microsomal Ca2+-ATPase. Biochemistry 24:7741-5
Anders, M W; Jakobson, I (1985) Biotransformation of halogenated solvents. Scand J Work Environ Health 11 Suppl 1:23-32
Aniya, Y; Anders, M W (1985) Chloroform-induced alteration of glutathione S-transferase activity. Biochem Pharmacol 34:249-55