TISSUE DISTRIBUTION OF DNA-ADDUCTS IN MALE FISCHER RATS EXPOSED TO 500 PPM OF PROPYLENE-OXIDE - QUANTITATIVE-ANALYSIS OF 7-(2-HYDROXYPROPYL)GUANINE BY P-32 POSTLABELING

7-(2-Hydroxypropyl)guanine (7-HPG) constitutes the major adduct from a lkylation of DNA by the genotoxic carcinogen, propylene oxide. The lev els of 7-HPG in DNA of various organs provides a relevant measure of t issue dose. 7-Alkylguanines can induce mutation through abasic sites f ormed from spontaneous depurination of the adduct. In the current stud y the formation of 7-HPG was investigated in male Fisher 344 rats expo sed to 500 ppm of propylene oxide by inhalation for 6 h/day, 5 days/we ek, for up to 20 days. 7-HPG was analyzed using the P-32-postlabelling assay with anion-exchange cartridges for adduct enrichment. In animal s sacrificed directly following 20 days of exposure, the adduct level was highest in the respiratory nasal epithelium (98.1 adducts per 10(6 ) nucleotides), followed by olfactory nasal epithelium (58.5), lung (1 6.3), lymphocytes (9.92), spleen (9.26), liver (4.64), and testis (2.9 5). The nasal cavity is the major target for tumor induction in the ra t following inhalation. This finding is consistent with the major diff erence in adduct levels observed in nasal epithelium compared to other tissues. In rats sacrificed 3 days after cessation of exposure, the l evels of 7-HPG in the aforementioned tissues had, on the average, decr eased by about one-quarter of their initial concentrations. This degre e of loss closely corresponds to the spontaneous rate of depurination for this adduct (t(1/2) = 120 h), and suggests a low efficiency of rep air for 7-HPG in the rat. The postlabelling assay used had a detection limit of one to two adducts per 10(8) nucleotides, i.e. it is likely that this adduct could be analyzed in nasal tissues of rats exposed to less than 1 ppm of propylene oxide. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.