Oxidative stress and 8-hydrodeoxyguanosine in rats following acute exposure to trichloroethylene or perchloroethylene.
Toraason-M; Clark-J; Dankovic-D; Mathias-P; Skaggs-S; Walker-C; Werren-D
Toxicologist 1999 Mar; 48(1-S):203-204
8-Hydroxydeoxyguanosine (80HdG) is a product of DNA oxidation and has been employed in occupational studies as a marker of biologically effective dose. Trichloroethylene (TCE) and perchloroethylene (PERC) are used in the dry cleaning industry and their metabolism can produce reactive oxygen compounds with the potential to oxidize DNA. The objective of the present study was to determine if acute exposure to TCE or PERC caused oxidative DNA damage in rats that could be detected as an increase in lymphocyte 80HdG/dG or urinary excretion of 80HdG. Thiobarbaturic acid reactive substances (TBARS) and 8-epi-prostaglandin 2 alpha (8epiPGF2) were also measured as biomarkers of increased oxidative stress. Male Fisher rats were administered a single i.p. injection of 0, 100, 500, or 1000 mg/kg of PERC or TCE. Control rats received only vehicle (1:4 v/v of Alkamuls/water) and a positive control group received 100 mg/kg 2-nitropropane (2NP). Rats were sacrificed 24 hrs after dosing. In rats receiving 2NP or TCE, TBARS and the 80HdG/dG ratio were significantly elevated in liver. Lymphocyte 80HdG/dG was also elevated, but not significantly. In rats receiving 2NP, urinary excretion of 80HdG and 8epiPGF2 were significantly increased at 12 and 24 hrs. In rats receiving TCE, no change in urinary excretion of 8epiPGF2 was evident, but an increase in 80HdG was noted at 24 hr. Results indicate that a single high dose of TCE can result in detectable elevation in 80HdG. Despite an absence of statistically significant effects in rats receiving PERC, dose-dependent trends in several endpoints suggest a slight increase in oxidative stress.
Animal-studies; Laboratory-animals; Statistical-analysis; Analytical-methods; Analytical-chemistry; Exposure-assessment; Toxicology; Toxins; Toxic-materials; Dry-cleaning-solvents; Dry-cleaning-industry; DNA-damage; Oxidative-processes; Oxidation
The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana