Studies in gastric carcinogenesis. IV. O6-Methylguanine and its repair in normal and atrophic biopsy specimens of human gastric mucosa. Correlation of O6-alkylguanine-DNA alkyltransferase activities in gastric mucosa and circulating lymphocytes

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Abstract
DNA extracted from biopsies of normal or atrophic gastric mucosa obtained from 20 individuals was analysed for the presence of the precarcinogenic alkylation lesion O6-methylguanine by a recently developed, highly sensitive assay based on repair by the Escherichia coliO6-alkylguanine-DNA alkyltransferase (AGT) enzyme in competition with a radiolabelled oligonucleotide containing O6-methylguanine (O6-meG). With a limit of detection of 0.5 fmol O6-meG in 10 μg DNA, only one DNA sample (derived from a region of the stomach with advanced chronic atrophic gastritis) was found marginally positive, containing 0.52 fmol/10 μg DNA (8.3 × 10-8 mol O6-meG/mol guanine). Measurements of AGT in 49 biopsies of normal, atrophic, hyperplastic or dysplastic mucosa obtained from the gastric antrum or corpus of 18 individuals did not reveal any significant effects of mucosal Histology on AGT. The average AGT value found was 6.9 ± 3.5 (SD) fmol/μg DNA, which is lower than the values reported for a number of other human tissues (liver, small intestine and lung). Measurement of AGT levels in gastric mucosa and circulating lymphocytes of the same individuals revealed a psitive correlation (P < 0.005), suggesting that lymphocytes may serve as a useful surrogate marker for AGT activity in gastric mucosa in studies of the epidemiology of this important repair enzyme.

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