Department of Biochemistry, R. G. Kar Medical College and Hospital, Kolkata, West Bengal, India.
Animal Biochemistry Division, National Dairy Research Institute, Karnal, Haryana, India.
Chem Biol Interact. 2021 Aug 25;345:109531. doi: 10.1016/j.cbi.2021.109531. Epub 2021 May 28.
Genotoxicity has been identified as the main cause of infertility and a variety of cancers. The mechanisms affect the structure, quality of the information or the segregation of DNA and are not inherently correlated with mutagenicity. The concept of genotoxicity, the chemical classes that cause genetic damage and the associated mechanisms of action are discussed here. Hazardous effects of pharmaceuticals, cosmetics, agrochemicals, industrial compounds, food additives, natural toxins and nanomaterials are, in large part, identified by genotoxicity and mutagenicity tests. These are critical and early steps in industrial and regulatory health assessment. Though several in vitro experiments are commonly used and approval by regulatory agencies for commercial licensing of drugs, their accuracy in human predictions for genotoxic and mutagenic effects is frequently questioned. Treatment of real and functional genetic toxicity problems depends in detail on the knowledge of mechanisms of DNA damage in the molecular, subcellular, cellular and tissue or organ system levels. Current strategies for risk assessment of human health need revisions to achieve robust and reliable results for optimizing their effectiveness. Additionally, computerized methods, neo-biomarkers leveraging '-omics' approaches, all of which can provide a convincing genotoxicity evaluation to reduce infertility and cancer risk.
遗传毒性已被确定为导致不孕和多种癌症的主要原因。其作用机制会影响 DNA 的结构、质量或分离，并且与致突变性并无内在关联。本文讨论了遗传毒性的概念、引起遗传损伤的化学类别以及相关的作用机制。药品、化妆品、农用化学品、工业化合物、食品添加剂、天然毒素和纳米材料的有害影响，在很大程度上是通过遗传毒性和致突变性测试来确定的。这些测试是工业和监管健康评估的关键和早期步骤。尽管有几种体外实验被广泛应用，并且监管机构也批准了药物的商业许可，但它们在人类预测遗传毒性和致突变性方面的准确性经常受到质疑。要解决实际的和功能性的遗传毒性问题，需要详细了解 DNA 损伤在分子、亚细胞、细胞和组织或器官系统水平上的机制。当前用于人类健康风险评估的策略需要进行修订，以获得稳健和可靠的结果，从而提高其有效性。此外，计算机化方法和利用“组学”方法的新型生物标志物都可以提供令人信服的遗传毒性评估，以降低不孕和癌症风险。
