Comparison of pulmonary DNA adduct levels, measured by 32P-postlabelling and aryl hydrocarbon hydroxylase activity in lung parenchyma of smokers and ex-smokers.
In order to compare pulmonary DNA adducts and aryl hydrocarbon hydroxylase (AHH) activity, we have measured these two parameters in non-neoplastic surgical lung parenchymal samples from four ex-smokers and 19 smokers, out of 20 patients operated for lung cancer, and three for nonmalignant lung diseases. DNA adducts were determined by scintillation counting after 32P-postlabelling analysis. The microsomal fractions of the same lung specimen were assayed for AHH activity by a fluorometric method. Autoradiograms of DNA adducts found in lungs of smokers revealed two distinct diagonal radioactive zones that were absent in ex-smokers. The smokers had significantly higher levels (1.68-13.4 DNA adducts/10(8) nucleotides; mean +/- SD 5.38 +/- 3.19) than ex-smokers (0.23-2.21; 1.09 +/- 0.84). AHH activity in smokers ranged from 0.01 to 0.69 pmol/min/mg. This activity was significantly (P less than 0.05) higher in smokers (0.26 +/- 0.26) who had smoked until 1 week before surgery than in those who had stopped smoking for greater than 7 days (0.11 +/- 0.11). A positive linear correlation between DNA adduct levels and AHH activity (r = 0.69; P less than 0.001; n = 19) was found in smokers. This relationship could explain why AHH inducibility appears to be a crude marker for lung cancer risk in smokers.
Geneste
O
O
International Agency for Research on Cancer, Lyon, France.
Camus
A M
AM
Castegnaro
M
M
Petruzzelli
S
S
Macchiarini
P
P
Angeletti
C A
CA
Giuntini
C
C
Bartsch
H
H
D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis*; D004247:DNA / Q000378:metabolism*; D005260:Female; D006801:Humans; D008168:Lung / Q000737:chemistry*; D008175:Lung Neoplasms / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010761:Phosphorus Radioisotopes; D012907:Smoking / Q000378:metabolism*
D010761:Phosphorus Radioisotopes; D004247:DNA; D001189:Aryl Hydrocarbon Hydroxylases