title: Mutagenicity of the mycotoxin alternariol in cultured mammalian cells.
abstract: The mycotoxin alternariol (AOH) is an important contaminant of fruit and cereal products. Concern about exposure to low levels of AOH was raised after the disclosure that contamination of food with the AOH-producing species Alternaria alternata is associated with oesophagal cancer. Previously we have reported that AOH induces kinetochore-negative micronuclei in cultured Chinese hamster V79 cells. The present study investigates the mutagenicity of AOH at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene locus in V79 cells and at the thymidine kinase (TK) gene locus in mouse lymphoma L5178Y tk(+/-) cells (MLC). Concentrations of 10 microM AOH and more gave rise to a significant and concentration-dependent induction of HPRT and TK mutations in V79 cells and in MLC, respectively. The mutagenic potency of AOH was about 50-fold lower than that of the established mutagen 4-nitroquinoline-N-oxide in both cell lines. Discrimination between small and large colonies in the TK assay revealed the predominant induction of small colonies, which are indicative for extensive chromosomal deletions and which correlated with the induction of micronuclei in MLC. The mutagenicity of AOH may have a bearing on the carcinogenicity of this mycotoxin.
authors.affiliation: Institute of Applied Biosciences, Section of Food Chemistry and Toxicology, University of Karlsruhe (TH), Kaiserstrasse 12, Karlsruhe D-76131, Germany.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Brugger
authors.forename: Jörg
authors.initials: J
authors.lastname: Wagner
authors.forename: David M
authors.initials: DM
authors.lastname: Schumacher
authors.forename: Karen
authors.initials: K
authors.lastname: Koch
authors.forename: Joachim
authors.initials: J
authors.lastname: Podlech
authors.forename: Manfred
authors.initials: M
authors.lastname: Metzler
authors.forename: Leane
authors.initials: L
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007783:Lactones / Q000633:toxicity*; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D009183:Mycotoxins / Q000633:toxicity*; D013937:Thymidine Kinase / Q000235:genetics*
chemical_list: D007783:Lactones; D009153:Mutagens; D009183:Mycotoxins; D007041:Hypoxanthine Phosphoribosyltransferase; D013937:Thymidine Kinase; C005197:alternariol