O-6-methylguanine-DNA methyltransferase (MGMT) plays an important role
in the repair of DNA lesions induced by alkylating carcinogens in a w
ide range of animals. To determine the relationship between DNA repair
activity and tumor susceptibility with advancing age the activity of
MGMT was measured in normal lung tissue extracts from 66 patients with
primary or metastatic lung cancer obtained at surgery. The age of the
patients whose lung MGMT activity was measured ranged from 40 to 79 y
ears (males) and from 40 to 80 years (females), and the values varied
over 10-fold in both sexes (33 males and 33 females). Our results indi
cate that the MGMT enzyme protein is expressed at appreciable levels t
hroughout life, and on age-associated rapid decline is not a feature i
n the human lung. Thus, any age-associated increase in lung cancer inc
idence cannot be ascribed to any change in MGMT activity. In order to
assess other possible factors which might exert a modulating influence
we examined the MGMT activity in relation to sex, tumor type and smok
ing. However, in none of these cases was any significant correlation e
vident.