title: Polychlorinated biphenyls induce meiotic length mutations at the human minisatellite MS32 in yeast.
abstract: Polychlorinated biphenyls (PCBs) are lipophilic compounds, several of which are toxic and carcinogenic. Complex mixtures of PCBs (e.g., Aroclor) have been widely used in the industry. The persistence of PCBs, in combination with poor waste management, has led to a large-scale distribution of PCBs in the biosphere. The toxic and carcinogenic effects of PCBs are poorly understood, but are suggested to be associated with Ah receptor binding and induction of the Ah-gene battery. We have previously shown that a higher-chlorinated PCB mixture, Aroclor 1254, significantly increased the germline mutation rate at the mouse minisatellite PC-1. We have recently developed an in vitro model system to study and characterize spontaneous and induced meiotic mutations in human minisatellites integrated in yeast. Here, for the first time, we have used this model system to show that chemicals, in this case Aroclor 1254, can induce meiotic length mutations at the human minisatellite MS32 in a yeast strain harboring 38- and 42-repeat-unit alleles. The results also show that the size distribution of mutant MS32 alleles differs between PCB and the control, with a larger proportion of mutant allele sizes below 29 repeat units in the PCB series. These alleles were not structurally different from the alleles of the same size in the control. We conclude that PCBs induce minisatellite mutations in meiosis and have recombinogenic properties, and that the mutations are induced in an Ah receptor-independent manner. The induction of minisatellite mutations in meiosis as an indication of genomic damage must be taken into account in the risk assessment of PCBs and other environmental contaminants.
authors.affiliation: Department of Genetic Toxicology, Wallenberg Laboratory, Stockholm University, Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Appelgren
authors.forename: M
authors.initials: M
authors.lastname: Hedenskog
authors.forename: C
authors.initials: C
authors.lastname: Sandström
authors.forename: H
authors.initials: H
authors.lastname: Cederberg
authors.forename: U
authors.initials: U
authors.lastname: Rannug
mesh_terms: D000483:Alleles; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D006801:Humans; D008540:Meiosis; D018895:Microsatellite Repeats / Q000187:drug effects*; D009152:Mutagenicity Tests / Q000379:methods*; D009154:Mutation; D011078:Polychlorinated Biphenyls / Q000633:toxicity; D016133:Polymerase Chain Reaction / Q000379:methods; D012091:Repetitive Sequences, Nucleic Acid; D015003:Yeasts / Q000187:drug effects / Q000235:genetics*
chemical_list: D020111:Chlorodiphenyl (54% Chlorine); D011078:Polychlorinated Biphenyls