Lack of binding of methapyrilene and similar antihistamines to rat liver DNA examined by 32P postlabeling.

Abstract

The nonmutagenic carcinogen methapyrilene, together with several noncarcinogenic analogues, was administered to rats p.o. for as long as 4 wk at concentrations of 0.1%. DNA was isolated from the liver and other organs and hydrolyzed, and the identification of covalent adducts was made using the 32P postlabeling method of Randerath. Some modified procedures were also used to deal with the possibility of very mobile adducts being formed from these hydrophilic amines. Although the rats had received as much as 2 g of amine per kg of body weight, no evidence of formation of DNA adducts in liver or other organs was seen; the level of detection was between 1 in 10(8) and 1 in 10(9) nucleotides. Adduct formation from much lower doses of the mutagenic food pyrolysis product 2-amino-3-methylimidaz(4, 5f)quinoline was detectable at a level of 1 in 10(6) nucleotides in parallel analyses. These results add to the evidence that carcinogenesis by methapyrilene is through an indirect or nonmutagenic mechanism.