根据国际癌症分类研究机构,甲醛是一种针对鼻腔的人类致癌物。在人类和大鼠中,吸入的甲醛主要沉积在鼻腔粘膜,代谢成毒性较小的甲酸,最后排入尿液或呼气。因此,甲醛引起的鼻腔致癌性可能是甲醛本身的直接作用,尽管潜在的机制仍不清楚.关于细胞毒性,短时间暴露于甲醛后,大鼠鼻呼吸道细胞发生变性和坏死。受损细胞的细胞增殖增加,提示其在鼻腔致癌的早期和整个过程中的关键作用。增生,鳞状上皮化生,受损上皮的异型增生常表现为形态学前兆病变。关于遗传毒性,除了DNA-蛋白质交联,氧化性DNA损伤也发生在暴露的鼻粘膜细胞中。持续暴露于甲醛可能通过细胞毒性和辅助遗传毒性引起鼻腔致癌性。在这次审查中,我们讨论了细胞毒性可导致致癌性的不良结局途径,以及非遗传毒性致癌物检测和评估的综合方法的发展.
According to the International Agency for Research on Cancer classification, formaldehyde is a human carcinogen that targets the nasal cavity. In humans and rats, inhaled formaldehyde is primarily deposited in the nasal cavity mucosa, metabolized to the less toxic formic acid, and finally excreted into the urine or exhaled. Thus, formaldehyde-induced nasal carcinogenicity may be a direct effect of formaldehyde itself, although the underlying mechanisms remain unclear. With regard to cytotoxicity, degeneration and necrosis of nasal respiratory cells occur in rats after short exposure to formaldehyde. Cell proliferation is increased in the damaged cells, suggesting its critical roles both in the early stages and throughout the entire process of nasal carcinogenicity. Hyperplasia, squamous metaplasia, and dysplasia of the damaged epithelium frequently appear as morphological precursor lesions. With regard to genotoxicity, in addition to DNA-protein crosslinks, oxidative DNA damage also occurs in the exposed nasal mucosal cells. Sustained exposure to formaldehyde may cause nasal carcinogenicity through cytotoxicity and auxiliary genotoxicity. In this
review, we discuss adverse outcome pathways through which cytotoxicity can lead to carcinogenicity and the development of integrated approaches for testing and assessment for nongenotoxic carcinogens.