Genetic effects of dioxins in the spot test with mice.

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.

Untitled

“…In the mouse spot test, there are four possible mechanisms by which the recessive coat-colour alleles can be expressed (see introduction) including gene and chromosome mutations. Although the chromosome mutations have to survive several mitoses to cause the expression of the recessive allele [118], there is evidence that also predominantly clastogenic substances might result in a positive mouse spot test. In contrast, the transgenic mutation assays detected point mutations and maximal small deletions and insertions [1].…”