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Article Publish Status: FREE
Abstract Title:

Low-dose formaldehyde delays DNA damage recognition and DNA excision repair in human cells.

Abstract Source:

PLoS One. 2014 ;9(4):e94149. Epub 2014 Apr 10. PMID: 24722772

Abstract Author(s):

Andreas Luch, Flurina C Clement Frey, Regula Meier, Jia Fei, Hanspeter Naegeli

Article Affiliation:

Andreas Luch

Abstract:

OBJECTIVE: Formaldehyde is still widely employed as a universal crosslinking agent, preservative and disinfectant, despite its proven carcinogenicity in occupationally exposed workers. Therefore, it is of paramount importance to understand the possible impact of low-dose formaldehyde exposures in the general population. Due to the concomitant occurrence of multiple indoor and outdoor toxicants, we tested how formaldehyde, at micromolar concentrations, interferes with general DNA damage recognition and excision processes that remove some of the most frequently inflicted DNA lesions.

METHODOLOGY/PRINCIPAL FINDINGS: The overall mobility of the DNA damage sensors UV-DDB (ultraviolet-damaged DNA-binding) and XPC (xeroderma pigmentosum group C) was analyzed by assessing real-time protein dynamics in the nucleus of cultured human cells exposed to non-cytotoxic (<100μM) formaldehyde concentrations. The DNA lesion-specific recruitment of these damage sensors was tested by monitoring their accumulation at local irradiation spots. DNA repair activity was determined in host-cell reactivation assays and, more directly, by measuring the excision of DNA lesions fromchromosomes. Taken together, these assays demonstrated that formaldehyde obstructs the rapid nuclear trafficking of DNA damage sensors and, consequently, slows down their relocation to DNA damage sites thus delaying the excision repair of target lesions. A concentration-dependent effect relationshipestablished a threshold concentration of as low as 25 micromolar for the inhibition of DNA excision repair.

CONCLUSIONS/SIGNIFICANCE: A main implication of the retarded repair activity is that low-dose formaldehyde may exert an adjuvant role in carcinogenesis by impeding the excision of multiple mutagenic base lesions. In view of this generally disruptive effect on DNA repair, we propose that formaldehyde exposures in the general population should be further decreased to help reducing cancer risks.

Study Type : In Vitro Study
Additional Links
Anti Therapeutic Actions : Vaccination: All : CK(12676) : AC(1344)
Problem Substances : Formaldehyde : CK(68) : AC(38)

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