Selective accumulation of 8-hydroxy-2'-deoxyguanosine in the lung following acute treatment with benzo(a)pyrene.
Stedeford-T; Cardozo-Pelaez-F; Hover-C; Harbison-RD; Sanchez-Ramos-J
Toxicologist 2001 Mar; 60(1):382
The lung has been shown to be a target organ for the effects of Benzo[a]pyrene (B[a]P). 8-hydroxy-2'-deoxyguanosine (oxo8dG) is a mutagenic oxidized base formed in DNA during the metabolism of B[a]P by the peroxidase and prostaglandin H synthetase systems. The objective of this study was to determine the capacity to cleave oxo8dG in the lung, liver, and kidney by measuring the activity of 8-oxoguanosine DNA glycosylase (Ogg1),and whether exposure to B[a]P had an effect in this DNA repair system. Male Sprague-Dawley rats were administered 20 mg/kg B[a]P i.p., 2 times/day for 5 days. A 26% decrease in the capacity to remove oxo8dG was observed in lung tissue at 72 hours and recovered 20% above control values at 120 hours. The capacity of the liver and kidney remained at baseline for all time points analyzed. A 7-fold increase in oxo8dG was observed in the lung at 72 hours and returned to basal levels by 120 hours. A statistically significant increase of Ogg1 protein levels was observed at 120 hours. Oxo8dG and Ogg1 protein levels were not significantly changed in the liver and kidney. This study demonstrates that organ-specific differences exist in the accumulation of oxo8dG and the capacity to remove this mutagenic base following i.p. treatment with B[a]P.
Lung; Liver; Kidneys; Laboratory-animals; Animals; Animal-studies; Exposure-levels; Exposure-assessment; Lung-tissue; DNA-damage; Benzopyrenes; Pyrenes
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California
University of South Florida