What are the DNA lesions underlying formaldehyde toxicity?

The simplest and most reactive naturally occurring aldehyde is formaldehyde (CH2O). It has been known since the 1940’s that formaldehyde reacts with both proteins and nucleic acids and can form intra- and intermolecular crosslinks between these macromolecules [1], [2], [3], [4]. Exposure to formaldehyde has been linked to a wide range of adverse health effects in humans, such as genotoxicity, carcinogenicity, and teratogenicity. The effect of formaldehyde on human health has been extensively studied and reviewed in many articles [5], [6], [7], [8], [9].

Formaldehyde is classified as a human carcinogen by the International Agency for Research on Cancer (IARC) based on the observation that formaldehyde inhalation can cause nasopharyngeal cancer in humans and squamous cell carcinomas in the nasal passages of rats [10]. However, the precise chemical nature of the nucleic acid lesions underlying formaldehyde toxicity in vivo remains elusive. Here, we review the current knowledge of the different types of damage induced by formaldehyde and describe the main repair pathways counteracting formaldehyde-induced lesions in cells.

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