METHYLGLYOXAL INDUCES HPRT MUTATION AND DNA-ADDUCTS IN HUMAN T-LYMPHOCYTES IN-VITRO

Methylglyoxal (MG) is a mutagen present in several foodstuffs, includi ng coffee. We have used the P-32-postlabelling method to measure MG-de oxygvanosine adduct levels, and the T-cell cloning technique, to study the frequency of hprt (hypoxanthine-guanine phosphoribosyl transferas e) mutant cells after treatment of human lymphocytes with MG in vitro. The mutant induction by single (18 hr) high-dose (1.0-1.5 mM) treatme nt was comparable to that induced by repeated (3 X 48 hr) low-dose (0. 1-0.4 mM) treatment. The latter also correlated with the adduct levels measured in the same experiment. The relative cell survival measured by direct cloning after the final treatment agreed well with the growt h curves monitored during the expression phase. Our results show that MG is capable of inducing hprt mutations as well as DNA adducts in hum an lymphocytes at doses with low cytotoxicity; However, significant ad duct formation (two- to threefold) could be obtained only after the fi rst exposure in cells subjected to a repeated treatment protocol, and the induced mutant frequency was low (two- to fourfold over background ). Thus, MG seems to be a comparatively weak mutagen in this system. ( C) 1995 Wiley-Liss, Inc.