Age and organ dependent spontaneous generation of nuclear 8-hydroxydeoxyguanosine in male Fischer 344 rats

8-Hydroxydeoxyguanosine (8-OHdG) is a major oxidative DNA adduct playing ro les in senescence, carcinogenesis and various disease processes. High-perfo rmance liquid chromatography with an electrochemical detection (HPLC-ECD) m ethod has been widely used to assess organ levels of 8-OHdG, and a recently introduced immunohistochemical approach has made it possible to clarify in tra-organ localization. In the present study, these methods were employed t o reveal age-dependent changes in nuclear 8-OHdG within various tissues of male Fischer 344 rats between 18 fetal days and 104 weeks of age. 8-OHdG wa s detected in the nuclei of cerebellar small granule and small cortical cel ls, cerebral nerve cells, and choroid plexus epithelia of the brain and epe ndymal cells of the spinal cord; parenchymal cells in the anterior lobe of the pituitary and adrenal glands (mainly cortex); bronchial epithelium of t he lung; intra-hepatic bile duct, pancreatic duct, glandular gastric and in testinal epithelial cells; renal tubular epithelial cells (mainly medulla); and spermatogonia and spermatocytes of the testis and seminal vesicle epit helia. The nuclear 8-OHdG levels were high (more than two lesions per 10(6) deoxyguanosines) from 7 days to 104 weeks of age in the brain, 3 to 6 week s in the adrenal gland, 6 to 104 weeks in the lung, and 3 to 52 weeks in th e testis. In the other organs, the nuclear 8-OHdG levels remained low throu ghout. These findings provide a basis for research dealing with oxidative s tress by indicating organ-specific and age- but not aging-dependent changes in the localization of spontaneously generated nuclear 8-OHdG in intact ra ts. The immunohistochemical approach has advantages for assessing variation of 8-OHdG formation at the cellular level not accessible to the HPLC-ECD m ethod.