Cell and tissue specific localization of O6-methylguanine in the DNA of rats given N-nitrosodimethylamine: effects of protein deficient and normal diets.

Abstract

An immunohistochemical procedure which is specific for the detection of O6-methylguanine (O6-MeG) in nuclear DNA has been used to examine tissues of rats after treatment with N-nitrosodimethylamine. In liver, the principal cells that are positive for O6-MeG are the centrilobular hepatocytes and the sinusoidal cells. In the kidney cortex the proximal tubules, the mesenchymal elements and the capsules of Bowman are positive, whilst the cells of the glomeruli and the renal medulla are negative. Maintaining the animals on a protein-free diet prior to treatment with the nitrosamine significantly reduces the width of the band of positive cells around the central vein in the liver and increases the number and intensity of positively staining cells in the renal cortex. Subject to subsequent modification by DNA repair and DNA replication, the procedure therefore identifies cells which are potential targets for nitrosamine induced toxicity and carcinogenicity in liver and kidney.