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 pg/kg for PCCD 2, 314 ,ug/kg for PCDD 1, and 3 fig/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 land 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.

Follicular Epithelial Cell Hypertrophy Induced by Chronic Oral Administration of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Female Harlan Sprague—Dawley Rats

“…Although TCDD is thought to be a multi-organ carcinogen, the compound is believed to be nongenotoxic (Fahrig, 1993;Geiger and Neal, 1981). In the recent NTP investigation of TCDD (National Toxicology Program, 2004), groups of rats treated with the highest dose of TCDD for 30 weeks and 30 weeks plus vehicle until the termination of the study (stop group) were examined to test the hypothesis that a relatively shorter period of TCDD treatment cannot promote tumorigenesis.…”