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.