Skip to main content
Log in

Depletion of nasal mucosal glutathione by acrolein and enhancement of formaldehyde-induced DNA-protein cross-linking by simultaneous exposure to acrolein

  • Original Investigations
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Referrence

  • ACGIH (1985) Threshold limit values for chemical substances and physical agents in the work environment and biological exposure indices with intended changes for 1984–85. American Conference of Governmental Industrial Hygienists, Cincinnati,Ohio, p 9

  • Alarie Y (1973) Sensory irriation by airborne chemicals. CRC Crit Rev Toxicol 2: 299–363

    Google Scholar 

  • Bailey RA, Clark HM, Ferris JP, Krause S, Strong RL (1978) Chemistry of the Environment, Academic Press, New York, p 268

    Google Scholar 

  • Barrow CS, Steinhagen WH (1982) Design, contruction and operation of a simple inhalation exposure system. Fundam Appl-Toxicol 2: 33–37

    Google Scholar 

  • Beauchamp RO, Jr, Morgan KT, Kligerman AD, Andjelkovich DA, Heck Hd'A (1985) A critical review of the literature on acrolein toxicity. CRC Crit Rev Toxicol 14: 309–380

    Google Scholar 

  • Casanova-Schmitz M, Heck Hd'A (1983) Effects of formaldehyde exposure on the extractability of DNA from proteins in the rat nasal mucosa. Toxicol Appl Pharmacol 70: 121–132

    Google Scholar 

  • Casanova-Schmitz M, Heck Hd'A (1985) DNA-protein crosslinking induced by formaldehyde (FA) in the rat respiratory mucosa: dependence on FA concentration in normal rats and in rats depleted of glutathione (GSH). Toxicologist 5: 128 (Abst. #509)

    Google Scholar 

  • Casanova-Schmitz M, David RM, Heck Hd'A (1984a) Oxidation of formaldehyde and acetaldehyde by NAD+-dependent dehydrogenases in rat nasal mucosal homogenates. Biochem Pharmacol 33: 1137–1142

    Google Scholar 

  • Casanova-Schmitz M, Starr TB, Heck Hd'A (1984b) Differentiation between metabolic incorporation and covalent binding in the labeling of macromolecules in the rat nasal mucosa and bone marrow by inhaled [14C]- and [3H] formaldehyde. Toxicol Appl Pharmacol 76: 26–44

    Google Scholar 

  • Chung FL, Young R, Hecht SS (1984) Formation of cyclic 1,N2-propanodeoxyguanosine adducts in DNA upon reaction with acrolein or crotonaldehyde. Cancer Res 44: 990–995

    Google Scholar 

  • Cohen IR, Altshuller AP (1961) A new spectrophotometric method for the determination of acrolein in combustion gases and in the atmosphere. Anal Chem 33: 726–733

    Google Scholar 

  • Connor TH, Barrie MD, Theiss JC, Matney TS, Ward JB Jr (1983) Mutagenicity of formalin in the Ames assay. Mutat Res 119: 145–149

    Google Scholar 

  • Dawson JR, Norbeck K, Anundi I, Moldéus P (1984) The effectiveness of N-acetylcysteine in isolated hepatocytes, against the toxicity of paracetamol, acrolein, and paraquat. Arch Toxicol 55: 11–15

    Google Scholar 

  • Downie NM, Heath RW (1970) Basic Statistical Methods, 3rd Edit., Harper & Row, New York, pp 221–222

    Google Scholar 

  • Esterbauer H, Zollner H, Scholz N (1975) Reaction of glutathione with conjugated carbonyls Z Naturforsch 30: 466–473

    Google Scholar 

  • Feron VJ, Kruysse A (1977) Effects of exposure to acrolein vapor in hamsters simultaneously treated with benzo[a]pyrene or diethynitrosamine. J Toxicol Environ Hlth 3: 379–394

    Google Scholar 

  • Hinegardner RT (1971) An improved fluorometric assay for DNA. Anal Biochem 39: 197–201

    Google Scholar 

  • Kane L, Alarie Y (1978) Evaluation of sensory irritation from acrolein-formaldehyde mixtures. Am Ind Hyg Assoc J 39: 270–274

    Google Scholar 

  • Kerns WD, Pavkov KL, Donofrio DJ, Gralla EJ, Swenberg JA (1983) Carcinogenicity of formaldehyde in rats and mice after long-term inhalation exposure. Cancer Res 43: 4382–4392

    Google Scholar 

  • Newsome JR, Norman V, Keith CH (1965) Vapor phase analysis of tobacco smoke. Tobacco Sci 9: 102–110

    Google Scholar 

  • Patel JM, Ortiz E, Kolmstetter C, Leibman KC (1984) Selective inactivation of rat lung and liver microsomal NADPH-cytochrome c reductase by acrolein. Drug Metab Disp 12: 460–463

    Google Scholar 

  • Ross WE, Shipley N (1980) Relationship between DNA damage and survival in formaldehyde-treated mouse cells. Mutat Res 79: 277–283

    Google Scholar 

  • Sedlak J, Lindsay RH (1968) Estimate of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem 25: 192–205

    Google Scholar 

  • Schauenstein E, Esterbauer H, Zollner H (1977) Aldehydes in biological systems — their natural occurrence and biological activities, Pion Limited, London, pp 25–32

    Google Scholar 

  • Temcharoen P, Thilly WG (1983) Toxic and mutagenic effects of formaldehyde in Salmonella typhimurium. Mutat Res 119: 89–93

    Google Scholar 

  • Uotila L, Koivusalo M (1974) Formaldehyde dehydrogenase from human liver. Purification, properties, and evidence for the formation of glutathione thiol esters by the enzyme. J Biol Chem 249: 7653–7663

    Google Scholar 

  • Zitting A, Heinonen T (1980) Decrease of reduced glutathione in isolated rat hepatocytes caused by acrolein, acrylonitrile, and the thermal degradation products of styrene copolymers. Toxicology 17: 333–341

    Google Scholar 

  • Zollner H, Esterbauer H, Schauenstein E (1975) Zusammenhang zwischen chemischer Konstitution und therapeutischer Wirkung a,β-ungesättigter Aldehyde am Ehrlich-Solid-Tumor der Maus. Z. Krebsforsch 83: 27–30

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lam, CW., Casanova, M. & Heck, H.d. Depletion of nasal mucosal glutathione by acrolein and enhancement of formaldehyde-induced DNA-protein cross-linking by simultaneous exposure to acrolein. Arch Toxicol 58, 67–71 (1985). https://doi.org/10.1007/BF00348311

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00348311

Key words

Navigation