The lack of binding of methyl-n-amyl ketone (MAK) to rat liver DNA as demonstrated by direct binding measurements, and P-32-postlabeling techniques

It has been reported that C-14-labeled methyl-n-amyl ketone (MAK, 2-heptano ne) is able to bind spontaneously, in vitro, to isolated rat liver DNA to t he extent of 400 pmol/mg DNA; and that C-14-MAK, when given by gavage to fe male Fischer 344 rats, resulted in HPLC chromatograms of isolated, hydrolyz ed liver DNA in which some radiolabel was not associated with the four norm al DNA bases dA, dT, dC, and dG. The present studies were undertaken to re- examine the hypothesis that MAK is able to bind to rat liver DNA. In the in vitro study, liver nuclear DNA was incubated with [2-C-14]-labeled MAK (25 mCi/mmol) in the absence, or in the presence of rat liver microsomes, prec ipitated, washed free of unbound MAK, and counted by scintillation spectrom etry. No binding to DNA by MAK was detectable. In the in vivo study, groups of five female F344 rats were exposed by inhalation to 0, 80, 400, or 1000 ppm MAK for 6 h/day for 10 days. DNA was purified from the liver nuclei of the 0 and 1000 ppm dosed animals, and P-32-postlabeling techniques were us ed to assay for adducts. No DNA adducts were detected using these technique s. It was concluded that MAK lacks the ability to bind to rat liver DNA in vitro and in vivo. (C) 1999 Elsevier Science B.V. All rights reserved.