Covalent binding of [14C]‐2,6‐dimethylaniline to DNA of rat liver and ethmoid turbinate

Abstract
The xylidide 2,6-dimethylaniline (2,6-DMA) has produced carcinomas and papillary adenomas in the nasal cavitiy of rats at high dietary doses (3000 ppm) in a 2-yr bioassay. The objective of the present study was to measure the covalent binding of 2,6-DMA to DNA of rat ethmoid turbinate tissues and, for comparison, to DNA of rat liver. The potent hepatocarcinogen 2-acetylaminofluorene (AAF) was studied as a positive control for adduct formation and covalent binding index (CBI) calculation. Both 2,6-DMA and AAF were administered as 14C-(ring)-labeled agents to naive rats and to rats pretreated for 9 with unlabeled 2,6-DMA or AAF. The CBI value for 2,6-DMA adduct formation with ethmoid turbinate DNA was below the assay''s sensitviity limit in nonpretreated rats, but increased to 41.9 in rats pretreated with unlabeled 2,6-DMA. It also increased from 0.6 in nonpretreated to 7.9 in liver of pretreated rats. The opposite pattern, however, was observed for AAF. In non-pretreated rats considerable adduct formation was observed in liver (CBI = 271.5) and modest values (CBI = 39.3) were calculated for ethoid turbinate tissues. Pretreatment with unlabeled AAF caused a significant decrease in CBI values, to 18.3 for liver and <0.5 for ethmoid turbinate.

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