Co-recombinogenic and anti-mutagenic effects of diethylhexylphthalate, inactiveness of pentachlorophenol in the spot test with mice.
In in vivo experiments using the spot test with mice, diethylhexylphthalate (DEHP) was co-recombinogenic and anti-mutagenic. In two independent experiments, DEHP was able to increase in combination with ethylnitrosourea (ENU) the frequency of animals with spots of genetic relevance from about 12% (ENU alone) to about 15% (ENU+DEHP). This enhancement can be exclusively attributed to an enhancement of recombination. In historical as well as in current experiments, with astonishing accuracy, about 8% of all spots induced with ENU alone are black, near-white or twin spots, i.e., presumed products of reciprocal recombination. Under the influence of DEHP, about 20% of all colored spots were black, near-white or twin spots. These co-recombinogenic effects are very strong, considering that the low frequency of twin spots with 0.3% (historical ENU control) or 0.6% (current ENU control) after ENU treatment alone has been enhanced up to a frequency of 3%. While ENU alone induces about 14% light brown colored spots, depending exclusively on gene mutations, under the influence of DEHP the frequency was only 7%, i.e., DEHP was anti-mutagenic. Pentachlorophenol was ineffective in enhancing or reducing recombination or mutations. There was no difference between ENU and ENU+PCP treatment. Since a number of "non-genotoxic' carcinogens with tumor-promoting activities like D-limonene, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) have shown similar effects in the spot test, it is suggested that DEHP may have tumor-promoting activity in carcinogenicity tests.
Fahrig
R
R
Department of Genetics, Fraunhofer-Institute for Toxicology and Aerosol Research, Hannover, Germany.
Steinkamp-Zucht
A
A
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity*; D004051:Diethylhexyl Phthalate / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D051379:Mice; D010416:Pentachlorophenol / Q000633:toxicity*; D011247:Pregnancy; D011995:Recombination, Genetic / Q000187:drug effects*
D016587:Antimutagenic Agents; D002273:Carcinogens; D004051:Diethylhexyl Phthalate; D010416:Pentachlorophenol