Cigarette smoke is known to contain high concentrations of free radica
ls and oxidants. To examine the oxidative effect of cigarette smoking,
we subjected rats to inhalation of cigarette smoke, and measured cell
ular free glutathione, the degree of protein S-thiolation, and 8-oxo-2
'deoxyguanosine (oxo(8)dG) in DNA. Inhalation of the cigarette smoke f
or 30 days, three times a day, resulted in a significant decrease of t
he total free glutathione contents in tissues, especially in the lung.
Elevated levels of oxidized glutathione and protein S-thiolation were
observed in the lung but not in other tissues. Increased contents of
oxo(8)dG in DNA were found in all tissues analyzed. When rats were tre
ated with buthionine sulfoximine (BSO, 80 mg/kg/day) to deplete glutat
hione, the oxidative effect of cigarette smoking was greatly potentiat
ed. The effect of glutathione depletion was most evident in the lung.
Cigarette smoking for only 7 days resulted in extreme depletion of the
glutathione both in the lungs and in the liver of BSO-treated rats. F
urthermore, oxo(8)dG in DNA increased markedly, especially in lung. Th
e results verified that the lung is a primary target of cigarette smok
e-induced oxidative damage, and cigarette smoke exerts its oxidative e
ffects on the rest of the entire organs eventually. Our results indica
te that glutathione plays crucial roles in protecting proteins and DNA
from oxidation caused by cigarette smoking. (C) 1998 Elsevier Science
Inc.