O6-Alkylguanine-DNA alkyltransferase in normal colon tissue and colon cancer.
O6-Alkylguanine-DNA alkyltransferase (AGT) is a DNA repair protein that reverses alkylation damage produced by chloroethylnitrosoureas and is a major determinant of cellular resistance to adjuvant chemotherapy with these drugs. AGT activity was measured in 119 samples from 69 patients, including normal, tumor, and diseased tissue, and 42 patients in which both normal and tumor tissue were assayed. The activity varied among individuals, but there was no statistically significant difference in average AGT activity among tumor, normal, and diseased tissue, or between men and women, or between young and old patients (< 70 or > 70 years). Few (3/49) tumor samples showed an absence of AGT activity (Mer- phenotype). The results indicate that nearly all colon cancers have significant AGT activity, and adjuvant chloroethylnitrosoureas chemotherapy must be modified, perhaps by the use of AGT biochemical modulators, to overcome this natural drug resistance.
White
A
A
Long Island Jewish Medical Center, New Hyde Park, NY 11042, USA.
Kibitel
J
J
Garcia
Y
Y
Belanich
M
M
Yarosh
D
D
Wideroff
J
J
Levin
L
L
Held
D
D
Fuchs
A
A
Citron
M
M
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D003106:Colon / Q000201:enzymology*; D003110:Colonic Neoplasms / Q000201:enzymology*; D004260:DNA Repair; D005260:Female; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000378:metabolism*; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase
D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase