Cantelli-Forti G, Paolini M, Hrelia P
Department of Pharmacology, University of Bologna, Italy.
Environ Health Perspect. 1993 Oct;101 Suppl 3(Suppl 3):15-20. doi: 10.1289/ehp.93101s315.
Because of the potential environmental impact of pesticides and the large population potentially exposed, the effects of chronic exposure to pesticides need to be determined. Mutagenicity studies have been used to identify specific agents as potential carcinogens or other human health hazards. However, short-term tests are only theoretically correlated to carcinogenesis because their end points can measure only the genotoxic potential of chemicals, i.e., their activities as initiating agents in multistep carcinogenesis. The objective of our research presented here is to provide a comprehensive examination of the mechanism of toxicity of a series of pesticides. These are substances for which toxicity, at both the genetic and metabolic level, has not been adequately described. Preliminary results on a broad series of compounds belonging to different biological classes (herbicide, insecticide, fungicide) seem to indicate that pesticides are toxic but are poor initiating agents, as shown by negative or weak positive results on different genetic end points (gene mutations, DNA effects, and chromosome aberrations in vitro and in vivo). Immunochemical and biochemical studies, however, seem to indicate the cocarcinogenic and promoting potential of these chemicals. As an example, the genotoxic and biochemical effects induced by Fenarimol (a fungicide) are discussed. The results reported stress the importance of identifying chemicals that act at different levels of the multistep carcinogenesis process to ascertain the risk associated with exposure.
由于农药可能对环境产生影响，且可能有大量人群暴露其中，因此需要确定长期接触农药的影响。致突变性研究已被用于识别特定物质是否为潜在致癌物或其他对人类健康的危害。然而，短期测试仅在理论上与致癌作用相关，因为其终点只能测量化学物质的遗传毒性潜力，即它们在多步骤致癌过程中作为引发剂的活性。我们在此展示的研究目的是全面考察一系列农药的毒性机制。这些物质在遗传和代谢水平上的毒性尚未得到充分描述。对属于不同生物类别（除草剂、杀虫剂、杀菌剂）的一系列广泛化合物的初步研究结果似乎表明，农药具有毒性，但作为引发剂的作用较弱，这从不同遗传终点（体外和体内的基因突变、DNA效应和染色体畸变）的阴性或弱阳性结果中可以看出。然而，免疫化学和生物化学研究似乎表明这些化学物质具有协同致癌和促进作用的潜力。例如，文中讨论了粉锈宁（一种杀菌剂）诱导的遗传毒性和生化效应。报告的结果强调了识别在多步骤致癌过程不同水平起作用的化学物质以确定与接触相关风险的重要性。
