Decreased extractability of DNA from proteins in the rat nasal mucosa after acetaldehyde exposure.
Acetaldehyde and formaldehyde have been found to induce nasal cancer in two species of rodents. To understand the mechanism of carcinogenesis by acetaldehyde, studies were carried out to determine whether acetaldehyde can react with DNA in target tissues of the rat nasal cavity. When fresh homogenates of the nasal respiratory mucosa were incubated with acetaldehyde (distilled under N2) at concentrations of 10, 100, or 500 mM, followed by solubilization and extraction with a strongly denaturing aqueous-immiscible organic solvent mixture, a decrease was observed in the amount of DNA partitioned into the aqueous phase at the two higher acetaldehyde concentrations. The absent DNA was recovered from the interfacial layer by proteolytic digestion. Similarly, incubation of calf thymus nucleohistones with acetaldehyde (100, 300, Similarly, incubation of calf thymus nucleohistones with acetaldehyde (100, 300, or 1000 mM) or with formaldehyde (10, 30, or 100 mM) followed by precipitation of the DNA with H2SO4 and analysis of the supernatants by sodium dodecyl sulfate-polyacrylamide gel electrophoresis resulted in concentration-dependent decreases in the quantities of histone proteins released from the DNA. These results indicate that acetaldehyde as well as formaldehyde can form DNA-protein crosslinks in vitro. A single 6-hr exposure of male Fischer-344 rats to acetaldehyde (100, 300, 1000, or 3000 ppm) resulted in a significant increase relative to air-exposed controls in the percent interfacial DNA from the nasal respiratory mucosa at concentrations equal to or greater than 1000 ppm. No increase in the interfacial DNA from the olfactory mucosa was detected after a single 6-hr exposure (1000 or 3000 ppm), but a significant increase was found in rats hr/day for 5 days) to acetaldehyde (1000 ppm). Thus, evidence has been obtained hr/day for 5 days) to acetaldehyde (1000 ppm). Thus, evidence has been obtained for the formation of DNA-protein crosslinks by acetaldehyde in target tissues of the rat nasal cavity at concentrations similar to those that induced nasal cancer.
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D000079:Acetaldehyde / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D003432:Cross-Linking Reagents / Q000633:toxicity; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D009669:Nose Neoplasms / Q000139:chemically induced; D010545:Peroxides / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012119:Respiration / Q000187:drug effects
D003432:Cross-Linking Reagents; D010545:Peroxides; D011506:Proteins; D005557:Formaldehyde; D004247:DNA; D005978:Glutathione; D000079:Acetaldehyde