Genetic effects of dioxins in the spot test with mice

二恶英在小鼠斑点试验中的遗传效应

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Abstract

More than any other environmental chemicals, dioxins have been in the limelight of public interest for about 10 years. In addition to carcinogenicity, genetic risk is a cause for concern. Mutagenicity tests performed so far do not give a clear picture. The mutagenic potential of dioxins has to be considered weak or absent. Therefore, it seemed profitable to investigate comutagenicity and co-recombinogenicity of dioxins more thoroughly. The only useful method for investigating comutagenicity and co-recombinogenicity of dioxins in vivo is the spot test with mice. In this test system, a number of cocarcinogens and tumor promoters have shown comutagenic or co-recombinogenic effects. In the present study, tetrachlorodibenzo-p-dioxin (TCDD) and two environmental dioxin mixtures [pentachlorodibenzodioxin (PCDD) 1 and 2] were tested for genetic activity. Given alone, no mutagenic or recombinogenic effects could be observed. In combination with the carcinogenic mutagen ethyl nitrosourea (ENU) at concentrations of 128 micrograms/kg for PCCD 2, 314 micrograms/kg for PCDD 1, and 3 micrograms/kg for TCDD, a doubling of the genetic effectiveness of ENU was observed. The genetic risk can roughly be considered as 1:0.02 for TCDD:PCDD 2 and 1:0.01 for TCDD:PCDD 1. While PCDD 1 and 2 seem to enhance the mutagenic as well as the recombinogenic potential of ENU, TCDD showed mainly co-recombinogenic and antimutagenic activity. This characteristic indicates that TCDD is mainly a tumor promoter.

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