Furan is not genotoxic in the micronucleus assay in vivo or in vitro.
Furan, a potential human carcinogen, is formed during heat-treatment of food. Previous studies of the genotoxicity of furan have given disparate results. Hence, there is a need for complementary data to clarify the mechanism behind the carcinogenicity of furan. In this study, we have used the flow cytometer-based micronucleus assay in mice and the cytokinesis-block micronucleus assay in human lymphocytes to investigate the genotoxic potential of furan. Three in vivo experiments were performed: intraperitoneal or subcutaneous injection of furan in male Balb/C mice (0-300 and 0-275 mg/kg body weight, respectively) and intraperitoneal injection of male CBA mice (0 and 225 mg/kg body weight). No increased level of micronucleated erythrocytes was detected in any of the in vivo experiments. In the in vitro setup, human lymphocytes from two donors were treated with furan in concentrations from 0 to 100 mM, either with or without metabolic activation (liver homogenate from rat). In parity with the in vivo results there was no significant increase in the frequency of micronucleated cells here either. As neither the in vivo nor the in vitro studies disclose any significant increase in the micronucleus frequency after treatment with furan, our results support that the carcinogenicity of furan is caused by a non-genotoxic mechanism.
Durling
Louise J K
LJ
Livsmedelsverket, National Food Administration, Toxicology Division, Box 622, SE-751 26 Uppsala, Sweden.
Svensson
Kettil
K
Abramsson-Zetterberg
Lilianne
L
D000328:Adult; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D005434:Flow Cytometry; D005663:Furans / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D015162:Micronucleus Tests; D008875:Middle Aged; D009153:Mutagens
D002273:Carcinogens; D005663:Furans; D009153:Mutagens; C039281:furan