Heavy metals are widely used in many industries in Thailand and found in the environment. Occupational exposure to heavy metals is often chronic and caused by environmental contaminations, potentially leading to mutations and cancer. Although the genotoxic effects of occupational exposure to multiple heavy metals have been extensively studied, the findings regarding their genotoxicity are conflicting. In this study, we focused on investigating the genotoxic effects of certain heavy metals mixtures, including lead (Pb), copper (Cu), zinc (Zn), and tin (Sn), to which workers are exposed in the manufacturing industry. The cytokinesis-blocked micronucleus (CBMN) assay in peripheral blood lymphocytes was performed, and DNA damage was assessed by measuring tumour-associated protein levels and 8-hydroxy-2′-deoxyguanosine (8-OHdG) generated by oxidative stress that causes cytotoxicity. The occupational exposure group included 110 workers exposed to heavy metal mixtures and 105 matched control subjects. We found statistically significant differences in the blood Pb, Sn, and Cu levels between the exposed workers and the control subjects (p < 0.001). Analysis of micronuclei (MN) in peripheral blood lymphocytes revealed a significantly increased frequency of MN in exposed workers compared with that in control subjects (p<0.05). Non-smoking exposed workers were selected for 8-OHdG formation and mutant p53 tests, and significant differences in the mean plasma 8-OHdG concentration (p < 0.001) were found between the occupational exposure and the control group, but no differences were found in the levels of mutant p53. Thus, chronic exposure to different heavy metals causes genotoxic effects in humans. Furthermore, the CBMN assay and 8-OHdG formation can be used as surrogate biomarkers to identify and monitor groups with higher carcinogenic risk in the early stages of toxicity. In summary, our results indicate that mixtures of heavy metals (Pb, Sn, and Cu) in manufacturing industries pose an elevated health risk due to DNA damage.

重金属广泛应用于泰国的许多行业，并存在于环境中。重金属职业暴露通常是慢性的，由环境污染引起，可能导致突变和癌症。尽管已经广泛研究了职业接触多种重金属的遗传毒性影响，但有关其遗传毒性的研究结果是相互矛盾的。在这项研究中，我们重点研究了某些重金属混合物的遗传毒性影响，包括铅 (Pb)、铜 (Cu)、锌 (Zn) 和锡 (Sn)，工人在制造业中会接触到这些混合物。在外周血淋巴细胞中进行胞质分裂阻断微核 (CBMN) 测定，通过测量导致细胞毒性的氧化应激产生的肿瘤相关蛋白水平和 8-羟基-2'-脱氧鸟苷 (8-OHdG) 来评估 DNA 损伤。职业暴露组包括 110 名暴露于重金属混合物的工人和 105 名匹配的对照对象。我们发现暴露工人和对照组之间的血液 Pb、Sn 和 Cu 水平存在统计学显着差异（p < 0.001)。外周血淋巴细胞微核 (MN) 分析显示，与对照组相比，暴露工人的 MN 频率显着增加（p<0.05）。选择非吸烟暴露工人进行 8-OHdG 形成和突变 p53 测试，平均血浆 8-OHdG 浓度差异显着（p< 0.001) 在职业暴露组和对照组之间发现，但在突变 p53 的水平上没有发现差异。因此，长期接触不同的重金属会对人类产生遗传毒性作用。此外，CBMN 测定和 8-OHdG 形成可用作替代生物标志物，以识别和监测毒性早期致癌风险较高的群体。总之，我们的结果表明，制造业中的重金属（Pb、Sn 和 Cu）混合物会由于 DNA 损伤而增加健康风险。