Cell specific DNA alkylation in traget and non-target organs of N-nitrosobis(2-oxopropyl)amine-induced carcinogenesis in hamster and rat

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Abstract
Tissue-specific formation and short-term persistence of alkylated DNA bases have been studied immunocytochem ically in Syrian hamsters and rats killed 3–48 h after a single s.c. or oral dose of N-nitrosobis(2-oxopropyl)amine (BOP). Antisera specific for O6-(m)ethlguanine and for 7-(m)ethylguanine were used. Strong naclear staining, indicative of a high level of DNA alkylation, was observed at all time points in the intra- and interlobular duct cells and in the centroacinar cells of the hamster pancreas, the main target organ of BOP-induced carcinogenesis. Acinar cells were wealdy stained for up to 24 h. In the liver, nudear staining was strong in all cell types, and more pronounced in the periportal than in the central venous area. Both O6 guanine and 7-alkylguanine preferentially disappeared from the centrilobular area of the liver which is in agreement with the high O6 activity of liver and the unusually high levels of 7-methylguanine DNA glycosylase activity in hamster tissues. Strong staining was observed throughout the experiment In the tubular cells of the renal cortex and in bronchiolar Clara and alveolar type II cells of the lung. The staining intensity of the cells of the thyroid follicles and of the columnar epithelial cells of the colon was moderate. hi the rat, nuclear staining was strong in the nasal cavity (Bowman glands), the epitheliwn lining the thyroid follicles, the lung, liver and in the fibroblasts of the ureter intima and adventitia. The epithelial cell nuclei of the colon and ureter were moderately stained, In the pancreas, staining was weak in adnar, duct and islet cells; no acinar staining remained at 48 h. In the liver, nuclear staining was strong all over the lobule. O was preferentially removed from the centrilobular area. The renal tubular cells were only weakly stained. From the present study we can conclude that-with the exception of hamster kidney and rat liver-high levels of DNA alkylation and stability of the alkylated products were related to a high tumor incidence.

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