O-6-METHYLGUANINE IN BLOOD LEUKOCYTE DNA - AN ASSOCIATION WITH THE GEOGRAPHIC PREVALENCE OF GASTRIC-CANCER AND WITH LOW-LEVELS OF SERUM PEPSINOGEN-A, A MARKER OF SEVERE CHRONIC ATROPHIC GASTRITIS

Using a competitive repair assay, 407 samples of peripheral blood leuc ocyte DNA from randomly selected subjects in 17 populations were teste d for the presence of the adduct O-6-methylguanine. With a limit of as say sensitivity of 0.05 fmol/mu g DNA, the adduct was detected in 21 s amples (5%). Sixteen positive samples came from 102 tested (16%) from two populations, in Japan and Portugal, with extremely high gastric ca ncer rates. This was significantly higher (P < 0.001) than the three p ositive samples out of 216 tested (1%) from populations with low or in termediate rates of gastric cancer. There was also an association betw een presence of the adduct and having a low (< 25 ng/ml) level of seru m pepsinogen A, a marker of severe chronic atrophic gastritis. These r esults are consistent with the general involvement of methylating agen ts in the pathogenesis of gastric cancer and with the model proposing formation of such compounds by endogenous nitrosation in the hypochlor hydric stomach.