Polycyclic aromatic hydrocarbon-DNA adducts in lung tissue from lung cancer patients.
In an attempt to probe for polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human subjects resulting from smoking (or other chronic environmental exposure), lung tissue and lung tumours were obtained from patients hospitalized for lung cancer. DNA was isolated from the tissue samples and examined both in an ELISA using a polyclonal antibody against (+/-)trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE)-DNA as well as by the nuclease P1-mediated modification of the 32P-post-labelling technique. The ELISA results showed BPDE-DNA antigenicity in lung DNA from 6 out of 21 patients, and adduct levels ranged from 2 to 134 adducts per 10(8) nucleotides. For all 21 patients, the autoradiographs of chromatograms of 32P-postlabelled digests of DNA from non-tumorous lung tissue showed a strong diagonal radioactive zone (DRZ). This DRZ was generally absent in tumorous tissue. DNA samples that were positive in the ELISA contained a dominant spot within the DRZ that co-chromatographed with the major BPDE-DNA adduct (BPDE-dG). The quantities of the BPDE-dG spots ranged from 2.1 to 42 adducts in 10(9) nucleotides. These values were lower than the levels found in the ELISA but correlated well with the ELISA results (Kendall W = 0.97; P = 0.00). The levels of the DRZ adducts ranged from 1.9 to 34 adducts in 10(8) nucleotides. Correlations between smoking and DNA adduct levels were poor because of the small number of current smokers (n = 13). However, smokers of filter cigarettes had significantly lower DNA adduct levels compared with smokers of cigarettes without a filter (P = 0.02 by Fischer's exact test).
van Schooten
F J
FJ
Division of Chemical Carcinogenesis, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam.
Hillebrand
M J
MJ
van Leeuwen
F E
FE
Lutgerink
J T
JT
van Zandwijk
N
N
Jansen
H M
HM
Kriek
E
E
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000032:analysis*; D001345:Autoradiography; D004247:DNA / Q000032:analysis*; D018736:DNA Adducts; D004273:DNA, Neoplasm / Q000032:analysis*; D004101:Dihydroxydihydrobenzopyrenes / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008168:Lung / Q000032:analysis*; D008175:Lung Neoplasms / Q000032:analysis*; D010761:Phosphorus Radioisotopes; D011083:Polycyclic Compounds / Q000032:analysis*; D012907:Smoking
D018736:DNA Adducts; D004273:DNA, Neoplasm; D004101:Dihydroxydihydrobenzopyrenes; D010761:Phosphorus Radioisotopes; D011083:Polycyclic Compounds; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA