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FORMATION OF CIGARETTE SMOKE-INDUCED DNA ADDUCTS IN THE RAT LUNG AND NASAL MUCOSA
Citation:
Gupta, R., M. Sopori, AND C. Gairola. FORMATION OF CIGARETTE SMOKE-INDUCED DNA ADDUCTS IN THE RAT LUNG AND NASAL MUCOSA. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-89/193.
Description:
The formation of DNA adducts in the nasal, lung, and liver tissues of rats exposed daily to fresh smoke from a University of Kentucky refernece cigarette (2R1) for up to 40 weeks was examined. he amount of smoke total particulate matter (TPM) inhaled and the blood carboxyhemoglobin (COHb) values averaged 5-5.5 mg smoke TPM/day/rat and 5.5%, respectivley. he pulmonary AHH activity measured as the termination of each experiment showed an average increase of about two- to threefold in the smoke-exposed groups. hese observations suggested that animals effectively inhaled both gaseous and particulate phase constituents of cigarette smoke. NAs from nasal, lung, and liver tissue were extracted and analyzed by an improved 32P-postlabeling procedure. he results showed that the mainstream cigarette smoke induced a spectrum of at least four new DNA adducts in the nasal mucosa of the exposed rats and the magnitude of these adducts increased with the duration of exposure. In the lung tissue, the smoke exposure induced an accumulation of one DNA adduct, which upon cessation of exposure for 19 weeks was reduced by about 75%. moke-related adducts were not detected in the liver, a nontarget tissue. elective chromatography and butanol extractability suggested that the nasal and lung DNA adducts are aromatic and/or hydrophobic in nature and that the smoke-related lung DNA-adduct may contain polar group(s). hese data demonstrate the DNA-damaging potential of long term fresh cigarette smoke exposure and suggest the ability of the tissue to partially recover from such damage following cessation of the exposure.