Genotoxicity analysis of N,N-dimethylaniline and N,N-dimethyl-p-toluidine.
N,N-Dimethylaniline (DMA, CAS No. 121-69-7) and N,N-dimethyl-p-toluidine (DMPT, CAS No. 99-97-8) belong to the N-dialkylaminoaromatics, a chemical class structurally alerting to DNA reactivity. Their applications may be industrial (dye and pesticide intermediates, polymerizing agents) and surgical (polymerization accelerators for the manufacture of bone cements and prosthetic devices), thus implying heterogeneous types of human exposure. Findings of carcinogenicity in rodents and some nonexhaustive genotoxicity data are available for DMA, but to our knowledge no information is available on DMPT concerning either carcinogenicity or any kind of genetic toxicity. To investigate their mechanism of action and mutagenic/carcinogenic potential, DMA and DMPT were analyzed for complementary genotoxicity endpoints, namely, gene mutation in Salmonella (Ames test), structural and numerical chromosome aberrations in hamster V79 cells (micronucleus test, matched with an immunofluorescent staining for kinetochore proteins), and in vivo DNA damage in mouse and rat liver (alkaline DNA elution test). The results essentially indicate that both chemicals are chromosome damaging agents. Indeed, at the maximum nontoxic doses, they proved nonmutagenic in Salmonella (although their toxicity did not allow concentrations > 70 micrograms/plate to be tested) and weakly positive in inducing DNA damage (increases in DNA elution rates at most approximately 2.4 times control value). Conversely, they proved clearly positive in inducing numerical chromosome alterations, with dose-dependent increases up to more than five times the control value for DMPT. At the highest dose tested, both chemicals also showed a significant clastogenic effect.
Institute of Oncology-CIRC, University of Genoa/National Institute for Cancer Research, Italy.
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Taningher
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Pasquini
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Bonatti
D000782:Aneuploidy; D000814:Aniline Compounds / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D002503:Centromere / Q000187:drug effects / Q000276:immunology; D016009:Chi-Square Distribution; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D005455:Fluorescent Antibody Technique; D008110:Liver Extracts; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015162:Micronucleus Tests; D008862:Microsomes, Liver / Q000201:enzymology; D008940:Mitotic Index; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D014052:Toluidines / Q000633:toxicity*
D000814:Aniline Compounds; D008110:Liver Extracts; D009153:Mutagens; D014052:Toluidines; C015157:N,N-dimethylaniline; C015835:dimethyl-4-toluidine