Investigations of the DNA-damaging activity of human gastric juice.
Human gastric juice previously treated with nitrite was examined for its ability to cause O6-alkylguanine-type modifications to 2'-deoxyguanosine or DNA in vitro. Analysis by radioimmunoassay indicated that, in five out of ten cases, incubation with 5 mM 2'-deoxyguanosine resulted in the formation of 375-1350 fmol/ml O6-ethyl-2'-deoxyguanosine (O6-etdGuo) or, in one case, 110 pmol/ml O6-methyl-2'-deoxyguanosine O6-medGuo). When gastric juice-treated calf-thymus DNA was examined for its ability to consume (through suicide repair of O6-alkylguanine-type damage) O6-alkylguanine-DNA alkyltransferase (AAT) from rat liver, eight out of eight samples could not. However, in four out of eight cases, a reduction in the rate of removal of O6-[3H]methylguanine from a 3H-methylated DNA substrate was observed. This finding is compatible with the presence, in gastric juice-treated DNA, of damage capable of binding to, but not undergoing repair by, the AAT.
Kyrtopoulos
S A
SA
National Hellenic Research Foundation, Institute of Biological Research, Athens, Greece.
D000818:Animals; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair; D003849:Deoxyguanosine / Q000032:analysis; D005745:Gastric Acidity Determination; D005750:Gastric Juice / Q000032:analysis* / Q000382:microbiology; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D006801:Humans; D008099:Liver / Q000201:enzymology; D008780:Methyltransferases / Q000378:metabolism; D009573:Nitrites / Q000009:adverse effects; D009602:Nitrosamines / Q000032:analysis / Q000652:urine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D011863:Radioimmunoassay; D051381:Rats
D009573:Nitrites; D009602:Nitrosamines; D006147:Guanine; C008449:O-(6)-methylguanine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D003849:Deoxyguanosine