Brominated flame retardants induce intragenic recombination in mammalian cells.

In the present study we have examined the effects of brominated flame retardants (BFR) and several other environmental contaminants in two in vitro assays for intragenic recombination at an endogenous locus in mammalian cells. A total ten compounds were investigated, i. e., two technical PCB mixtures (Aroclor 1221 and Aroclor 1254), DDT, PCP, tetrabromobisphenol A (TBBPA), 4,4'-bischlorophenyl sulfone (BCPS), hexabromocyclododecane (HBCD) and the three different polybrominated diphenylethers (PBDEs): 2-bromodiphenylether (MBDE), 3,4-dibromodiphenylether (DBDE) and 2,4,2', 4'-tetrabromodiphenylether (TBDE). In the SPD8 assay system statistically significant increases in recombination frequency were observed with Aroclor 1221, BCPS, DBDE, DDT, HBCD, MBDE and TBDE. In the Sp5 assay system, only DBDE, HBCD and MBDE caused statistically significant increases in recombination frequency. In conclusion, our findings indicate that the modern additives to plastic, i.e., HBCD and PBDEs, as well as the plastic monomer BCPS may have the same effect to human health as DDT and PCBs, in terms of inducing genetic recombination, which is known to provoke a number of diseases, including cancer.

[1]  D. Jenssen,et al.  Studies on intrachromosomal recombination in SP5/V79 Chinese hamster cells upon exposure to different agents related to carcinogenesis. , 1994, Carcinogenesis.

[2]  R. L. Carter,et al.  IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans , 1980, IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans.

[3]  Bo Jansson,et al.  Polybrominated diphenyl ethers and hexabromocyclododecane in sediment and fish from a Swedish River , 1998 .

[4]  J. Haseman,et al.  Comparative carcinogenicity of polybrominated biphenyls with or without perinatal exposure in rats and mice. , 1993, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[5]  B. N. Gupta,et al.  Effects of a polybrominated biphenyl mixture in the rat and mouse. II. Lifetime study. , 1983, Toxicology and applied pharmacology.

[6]  D. Jenssen,et al.  Characterization of mutants involving partial exon duplications in thehprt gene of Chinese hamster V79 cells , 1996, Somatic cell and molecular genetics.

[7]  T. Helleday,et al.  Effects of carcinogenic agents upon different mechanisms for intragenic recombination in mammalian cells. , 1998, Carcinogenesis.

[8]  A. Pijnenburg,et al.  Polybrominated biphenyl and diphenylether flame retardants: analysis, toxicity, and environmental occurrence. , 1995, Reviews of environmental contamination and toxicology.

[9]  J. Aubrecht,et al.  Polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin induce intrachromosomal recombination in vitro and in vivo. , 1997, Cancer research.

[10]  R. Schiestl Nonmutagenic carcinogens induce intrachromosomal recombination in yeast , 1989, Nature.

[11]  Å. Bergman,et al.  A new persistent contaminant detected in Baltic wildlife: bis(4-chlorophenyl) sulfone , 1995 .

[12]  M. Haugg,et al.  SYNTHESIS AND CHARACTERIZATION OF POLYBROMINATED DIPHENYL ETHERS : UNLABELLED AND RADIOLABELLED TETRA-, PENTA- AND HEXA-BROMODIPHENYL ETHERS , 1996 .

[13]  V. Jansson,et al.  Inability of chlorophenols to induce 6-thioguanine-resistant mutants in V79 Chinese hamster cells. , 1986, Mutation research.

[14]  M. Bauchinger,et al.  Chromosome changes in lymphocytes after occupational exposure to pentachlorophenol (PCP). , 1982, Mutation research.

[15]  D. Jenssen,et al.  Reversion of the hprt mutant clone SP5 by intrachromosomal recombination. , 1992, Carcinogenesis.

[16]  J. Boer,et al.  Polybrominated diphenylethers in human adipose tissue and relation with watching television - a case study , 1998 .

[17]  T. Helleday,et al.  A partial hprt gene duplication generated by non-homologous recombination in V79 Chinese hamster cells is eliminated by homologous recombination. , 1998, Journal of molecular biology.

[18]  B. Jansson,et al.  Analysis of tetrabromobisphenol A in a product and environmental samples , 1995 .

[19]  G. Kass,et al.  Mechanistic studies on the DDT-induced inhibition of intercellular communication. , 1989, Carcinogenesis.

[20]  M. O’Donovan Mutagenicity of some intercalating agents in Chinese hamster V79 cells. , 1984, Mutation research.

[21]  E. Pellizzari,et al.  Identification and Quantitation of Brominated Fire Retardants , 1979 .

[22]  J. Boer,et al.  Do flame retardants threaten ocean life? , 1998, Nature.

[23]  J. Trosko,et al.  Failure to induce mutations in Chinese hamster V79 cells and WB rat liver cells by the polybrominated biphenyls, Firemaster BP-6, 2,2',4,4',5,5'-hexabromobiphenyl, 3,3',4,4',5,5'-hexabromobiphenyl, and 3,3',4,4'-tetrabromobiphenyl. , 1985, Toxicology and applied pharmacology.

[24]  M. L. Hattula Mutagenicity of PCBs and their pyrosynthetic derivatives in cell-mediated assay. , 1985, Environmental health perspectives.

[25]  L. Robertson,et al.  Carcinogenicity of polyhalogenated biphenyls: PCBs and PBBs. , 1990, Critical reviews in toxicology.

[26]  V. J. Decarlo STUDIES ON BROMINATED CHEMICALS IN THE ENVIRONMENT , 1979, Annals of the New York Academy of Sciences.

[27]  J. Aubrecht,et al.  Carcinogens induce intrachromosomal recombination in human cells. , 1995, Carcinogenesis.

[28]  H. Cederberg,et al.  Induction of germline‐length mutations at the minisatellites PC‐1 and PC‐2 in male mice exposed to polychlorinated biphenyls and diesel exhaust emissions , 1997, Environmental and molecular mutagenesis.

[29]  J. Trosko,et al.  Inhibition of metabolic cooperation in Chinese hamster V79 cells in culture by various polybrominated biphenyl (PBB) congeners. , 1982, Carcinogenesis.

[30]  V. Burse,et al.  Induction of liver tumors in female Sherman strain rats by polybrominated biphenyls. , 1981, Journal of the National Cancer Institute.

[31]  E. Zeiger,et al.  Chromosome aberrations and sister chromatid exchanges in chinese hamster ovary cells: Evaluations of 108 chemicals , 1987, Environmental and molecular mutagenesis.