Local genotoxic effects of formaldehyde in humans measured by the micronucleus test with exfoliated epithelial cells.

摘要

Formaldehyde (FA) is genotoxic in vitro in cultured mammalian cells. When FA reaches the nuclear DNA, it forms DNA-protein cross-links (DPX). Incomplete repair of DPX can lead to the formation of mutations, in particular chromosome mutations and micronuclei (MN) in proliferating cells. Due to its high reactivity, FA leads primarily to local genotoxic effects at the site of contact. In humans, local genotoxic effects of FA have been studied with the micronucleus test (MNT) in exfoliated nasal and buccal mucosa cells. This approach is considered to be highly relevant because these tissues are the actual targets of FA, and MN are a sensitive indicator for the mutagenic action of FA. The published studies suggest that inhalation of FA leads to increased MN frequencies in nasal and/or buccal mucosa cells. However, a critical review of the data reveals that the effects are not consistent, and the studies should be interpreted with caution. One problem is the lack of standardization of the MNT with exfoliatedcells and the high assay variability. Another problem concerns the quality of published studies indicating local genotoxic effects of FA in humans. Incomplete information on study design, exposure, and confounding factors frequently limit the interpretation of these studies. On the basis of the available data, it is not yet possible to assess the local genotoxicity of FA in humans and to draw meaningful conclusions with regard to a dose-effect relationship for risk estimation.