Oxidative stress and DNA damage in Fischer rats following acute exposure to trichloroethylene or perchloroethylene.
Toraason-M; Clark-J; Dankovic-D; Mathias-P; Skaggs-S; Walker-C; Werren-D
Toxicology 1999 Oct; 138(1):43-53
Oxidative DNA damage is emerging as an biomarker of effect in studies assessing the health risks of occupational chemicals. Trichloroethylene (TCE) and perchloroethylene (PERC) are used in the dry cleaning industry and their metabolism can produce reactive oxygen compounds. The present study examined the potential for TCE and PERC to induce oxidative DNA damage in rats that was detectable as increased urinary excretion of 8-hydroxydeoxyguanosine (8OHdG). Thiobarbaturic acid reactive substances (TBARS) and 8-epi-prostaglandin F2a (8epiPGF) were also measured as biomarkers of increased oxidative stress. Male Fischer 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). A positive control group received 100 mg/kg 2-nitropropane (2NP). Rats were sacrificed 24 h after dosing. In rats receiving 2NP or TCE but not PERC, TBARS and the 8OHdG/dG ratios were significantly elevated in liver. Lymphocyte 8OHdG/dG was not affected significantly by 2NP, TCE or PERC. In rats receiving 2NP, urinary excretion of 8OHdG and 8epiPGF2 were significantly increased. In rats receiving TCE or PERC, significant increases in 8epiPGF2 or 8OHdG were not evident. Results indicate that a single high dose of TCE, but not PERC, can induce an increase in oxidative DNA damage in rat liver. However, the usefulness of 8OHdG as a biomarker of TCE-induced oxidative DNA damage is questionable.
Dry-cleaning-industry; Dry-cleaning-solvents; Laundering; Statistical-analysis; Cancer; Carcinogens; Carcinogenicity; Carcinogenesis; DNA-damage; Oxidation; Oxidation-reduction-reactions; Oxidative-processes; Laboratory-animals; Animal-studies; Animals; Urinalysis; Urine-chemistry; Mortality-rates; Mortality-data; Morbidity-rates; Lymphocytes
M. Toraason, The National Institute for Occupational Safety and Health, 4676 Columbia Parkway, Cincinnati, OH 45226, USA