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Formation of Cigarette Smoke-induced DNA Adducts in the Rat Lung and Nasal Mucosa¹

Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030 [R. C. G.]; Lovelace Biomedical Foundation, Albuquerque, New Mexico 87108 [M. L. S.]; and Tobacco and Health Research Institute and the Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40506 [C. G. G.]

The formation of DNA adducts in the nasal, lung, and liver tissues of rats exposed daily to fresh smoke from a University of Kentucky reference cigarette (2R1) for up to 40 weeks was examined. The 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%, respectively. The pulmonary AHH activity measured at the termination of each experiment showed an average increase of about two- to threefold in the smoke-exposed groups. These observations suggested that animals effectively inhaled both gaseous and particulate phase constituents of cigarette smoke. DNAs from nasal, lung, and liver tissue were extracted and analyzed by an improved ³²P-postlabeling procedure. The 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%. Smoke-related adducts were not detected in the liver, a nontarget tissue. Selective 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). These 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.

¹ This work was supported by the EPA Cooperative Agreement CR 813840 (R. C. G.), and by grants from USPHS [CA-30606 (R. C. G.), DA 04208-NIH CTR 157 (M. L. S.), and KTRB41031 (C. G. G.)].

² To whom requests for reprints should be addressed, at Tobacco and Health Research Institute, University of Kentucky, Lexington, KY 40546-0236.

Received 8/18/88. Revised 12/12/88. Accepted 1/18/89.

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