Do chromosome changes in blood cells implicate formaldehyde as a leukemogen?

Formaldehyde (FA) is a mutagenic chemical - a property mitigated in vivo by rapid detoxification and limited tissue distribution following inhalation of the free agent. Endogenously produced FA is necessary for life and required for one-carbon transfer reactions; however, FA derived from external sources (exogenous FA), which may be in the form of methanol, may increase in vivo concentrations above naturally occurring physiological levels. Both endogenous and exogenous FA produce DNA monoadducts, DNA-DNA and DNA-protein cross-links (DDX and DPX) but, when exposed to exogenously-derived free FA, DNA monoadducts, DDX, and DPX are only produced at initial sites of contact. In contrast, methanol may systemically induce DNA adducts distally. FA also induces oxidative stress/lipid peroxidation with some individuals suggesting the resulting reactive aldehydes may have the potential to induce distal site DNA damage with the resulting reactive aldehydes having the potential to induce distal site DNA damage. Chromosome changes in the form of aberrations or micronuclei in blood cells have been studied in FA-exposed animals and humans, with most of the former being negative. Human occupational studies have given mixed results for such changes in peripheral blood lymphocytes (PBLs) which circulate widely but do not reflect recent bone marrow (BM) events. Recent studies reporting changes in human BM or hematopoietic precursor cells (HPCs) either have had confounding exposures or could not distinguish in vivo from in vitro occurrences. The reported genetic changes in circulating blood cells do not provide convincing support for FA's classification as a human leukemogen.