Evaluation of the genotoxic potential of 3-monochloropropane-1,2-diol (3-MCPD) and its metabolites, glycidol and beta-chlorolactic acid, using the single cell gel/comet assay.
3-monochloropropane-1,2-diol (3-MCPD) is a member of a group of chemicals known as chloropropanols. It is found in many foods and food ingredients as a result of food processing. 3-MCPD is regarded as a rat carcinogen known to induce Leydig-cell and mammary gland tumours in males and kidney tumours in both genders. The aim of our study was to clarify the possible involvement of genotoxic mechanisms in 3-MCPD induced carcinogenicity at the target organ level. For that purpose, we evaluated DNA damages in selected target (kidneys and testes) and non-target (blood leukocytes, liver and bone marrow) male rat organs by the in vivo alkaline single cell gel electrophoresis (comet) assay, 3 and 24 h after 3-MCPD oral administration to Sprague-Dawley and Fisher 344 adult rats. 3-MCPD may be metabolised to a genotoxic intermediate, glycidol, whereas the predominant urinary metabolite in rats following 3-MCPD administration is beta-chlorolactic acid. Therefore, we also studied the DNA damaging effects of 3-MCPD and its metabolites, glycidol and beta-chlorolactic acid, in the in vitro comet assay on CHO cells. Our results show the absence of genotoxic potential of 3-MCPD in vivo in the target as well as in the non-target organs. Glycidol, the epoxide metabolite, induced DNA damages in CHO cells. beta-Chlorolactic acid, the main metabolite of 3-MCPD in rats, was shown to be devoid of DNA-damaging effects in vitro in mammalian cells.
El Ramy
R
R
Agence Française de Sécurité Sanitaire des Aliments, Unité de Toxicologie Génétique des Contaminants Alimentaires, la Haute Marche 35133 Javené, Fougères, France. r.elramy@fougeres.afssa.fr
Ould Elhkim
M
M
Lezmi
S
S
Poul
J M
JM
D000284:Administration, Oral; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D016466:CHO Cells; D002273:Carcinogens / Q000633:toxicity*; D020552:Comet Assay; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000633:toxicity*; D005990:Glycerol / Q000031:analogs & derivatives* / Q000633:toxicity; D007668:Kidney / Q000187:drug effects; D019344:Lactic Acid / Q000633:toxicity*; D007962:Leukocytes / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D020005:Propanols / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects; D000517:alpha-Chlorohydrin
D002273:Carcinogens; D004852:Epoxy Compounds; D009153:Mutagens; D020005:Propanols; D019344:Lactic Acid; D000517:alpha-Chlorohydrin; D005990:Glycerol; C004312:glycidol