Induction of chromosomal aberrations by phenolic compounds: possible role of reactive oxygen species.
Phenolic molecules are widely present in the environment and some of them are well known carcinogens. Some phenolic molecules are also genotoxic but the mechanisms involved in this process are not fully understood. We have studied the induction of chromosomal aberrations by phenol, catechol and pyrogallol in V79 cells at different pH values (6.0, 7.4 and 8.0). At the same pH values, the production of hydroxyl radicals was assessed by measuring the degradation of deoxyribose. Apart from phenol, which only induces a non-significant increase in chromosomal aberration in this experimental system, catechol and pyrogallol showed clear clastogenic effect in a pH-dependent way. Experiments carried out at pH 7.4 in the presence of S9 Mix, SOD, catalase and catalase + SOD suggest that the formation of reactive oxygen species is not the main mechanism involved in the genotoxicity of catechol. However, concerning pyrogallol, our results suggest that its genotoxicity is almost exclusively mediated by reactive oxygen species. Taken together, these results suggest that, in spite of the structural similarity between the different molecules studied, the mechanisms of genotoxicity of these molecules could be considerably different. The existence of several mechanisms of genotoxicity, partially shared by this class of compounds, could explain the synergistic effects observed between these compounds in several genotoxicity test systems. Accurate knowledge of their mechanisms of genotoxicity could improve considerably the assessment of their relevance to human health, since these compounds, once absorbed, are subject to a wide range of pH values in vivo.
do Céu Silva
Maria
M
Faculty of Medical Sciences, Department of Genetics, New University of Lisbon, Rua da Junqueira 96, P-1349-008 Lisboa, Portugal.
Gaspar
Jorge
J
Silva
Isabel Duarte
ID
Leão
Daniela
D
Rueff
José
J
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D002396:Catechols / Q000633:toxicity; D002869:Chromosome Aberrations; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D010636:Phenols / Q000633:toxicity*; D011748:Pyrogallol / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology
D002396:Catechols; D009153:Mutagens; D010636:Phenols; D017382:Reactive Oxygen Species; D011748:Pyrogallol; D002374:Catalase; D013482:Superoxide Dismutase; C034221:catechol