P53 MUTATIONS IN LUNG-TUMORS - RELATIONSHIP TO GENDER AND LUNG DNA ADDUCT LEVELS

Human lung cancer exhibits a high frequency of transversion mutations at G:C base pairs of the p53 gene, possibly the result of DNA damage b y cigarette smoke constituents, most notably benzo[a]pyrene. We have i nvestigated gender differences in the p53 mutational spectrum and leve ls of hydrophobic DNA adducts. Tumour tissue was obtained from 115 non -small cell lung cancer tumours and examined for mutational alteration s in the p53 gene (exons 4-9) using PCR and single-strand conformation al polymorphism analysis. We have previously examined exons 5-8 in lun g cancer. Sequence analysis of exons 4 and 9 revealed that almost 20% of the mutations were located in exons 4 and 9. The levels of hydropho bic DNA adducts in non-tumorous lung tissue of 55 of the patients Were analyzed by the P-32-postlabelling assay. There were both a higher fr equency of G:C-->T:A mutations and a higher average hydrophobic DNA ad duct level in females than in male patients, even though the level of exposure to carcinogens from cigarette smoking was lower among the fem ales than among the males, Frameshift mutations were more common in wo men than in men (30 versus 15%). These preliminary findings lend suppo rt to epidemiological evidence that women may be at greater risk than men of contracting tobacco-induced lung cancer.