O6-alkylguanine-DNA alkyltransferase activity in schistosomiasis-associated human bladder cancer.
O6-Alkylguanine-DNA-alkyltransferase (ATase) activity was measured in extracts of 55 bladder tissue samples (46 tumour and nine uninvolved mucosal tissue) from Egyptian patients with schistosome-associated bladder carcinoma. Activity varied from 2.0 to 16.2 fmole ATase/microgram DNA (mean +/- S.D.; 5.6 +/- 4.0) or from 28 to 351 fmole ATase/mg (117 +/- 71). ATase levels in schistosome-associated bladder cancer tissues (5.6 +/- 4.0 fmole ATase/microgram DNA) tended to be lower than those observed in normal human bladder mucosal tissue (8.5 +/- 4.4 fmole ATase/microgram DNA). In a previous study (Badawi et al., Carcinogenesis, 1992, 13, 877-881) DNA-alkylation damage (O6-methyldeoxyguanosine) was found in 44/46 of these schistosome-associated bladder cancer samples at levels ranging from 0.012 to 0.485 mumole O6-MedG/mole deoxyguanosine. We now report an inverse correlation between the levels of methylation damage and ATase activity (r = -0.67; P < 0.001). These observations encourage further investigations of the possible role of environmental alkylating agents in the aetiology of early bladder cancer associated with schistosomiasis.
Badawi
A F
AF
National Center for Toxicology, Jefferson, Arkansas.
Cooper
D P
DP
Mostafa
M H
MH
Aboul-Azm
T
T
Barnard
R
R
Margison
G P
GP
O'Connor
P J
PJ
D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D012553:Schistosomiasis haematobia / Q000150:complications* / Q000201:enzymology; D001743:Urinary Bladder / Q000201:enzymology; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000209:etiology
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase