Methylglyoxal induces hprt mutation and DNA adducts in human T-lymphocytes in vitro.
Methylglyoxal (MG) is a mutagen present in several foodstuffs, including coffee. We have used the 32P-postlabelling method to measure MG-deoxyguanosine adduct levels, and the T-cell cloning technique, to study the frequency of hprt (hypoxanthine-guanine phosphoribosyl transferase) 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) treatment 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 growth curves monitored during the expression phase. Our results show that MG is capable of inducing hprt mutations as well as DNA adducts in human lymphocytes at doses with low cytotoxicity. However, significant adduct formation (two- to threefold) could be obtained only after the first 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.
Hou
S M
SM
Environmental Medicine Unit, NOVUM, Karolinska Institute, Huddinge, Sweden.
Nori
P
P
Fang
J L
JL
Vaca
C E
CE
D000328:Adult; D000368:Aged; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D018736:DNA Adducts / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007093:Imidazoles / Q000032:analysis; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011765:Pyruvaldehyde / Q000633:toxicity*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D018736:DNA Adducts; D007093:Imidazoles; D009153:Mutagens; C098041:3-(2-deoxypentofuranosyl)-3,5,6,7-tetrahydro-6,7-dihydroxy-6-methyl-9H-imidazo(1,2-a)purin-9-one; D011765:Pyruvaldehyde; D007041:Hypoxanthine Phosphoribosyltransferase; D003849:Deoxyguanosine