Depletion of nasal mucosal glutathione by acrolein and enhancement of formaldehyde-induced DNA-protein cross-linking by simultaneous exposure to acrolein.
Incubation of homogenates of rat nasal mucosa with acrolein resulted in the apparent formation of DNA-protein cross-links. However, inhalation exposure of male Fischer-344 rats to acrolein (2.0 ppm, 6 h) did not cause detectable DNA-protein cross-linking in the nasal respiratory mucosa. Simultaneous exposure of rats to both acrolein (2.0 ppm) and formaldehyde (6.0 ppm) for 6 h resulted in a significantly higher yield of DNA-protein cross-links than was obtained following exposure to formaldehyde (6.0 ppm) alone. Acrolein exposure at concentrations of 0.1, 0.5, 1.0, or 2.5 ppm resulted in a concentration-dependent depletion of nonprotein sulfhydryl groups in the nasal respiratory mucosa. A plausible explanation for the enhancement of DNA-protein cross-links by simultaneous exposure to formaldehyde and acrolein may be that depletion of glutathione by acrolein inhibited the oxidative metabolism of formaldehyde, leading to an increase of formaldehyde-induced DNA-protein cross-links.
D000171:Acrolein / Q000494:pharmacology*; D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D004247:DNA / Q000378:metabolism*; D005557:Formaldehyde / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000447:Aldehydes; D011506:Proteins; D013438:Sulfhydryl Compounds; D005557:Formaldehyde; D000171:Acrolein; D004247:DNA; D005978:Glutathione