O6-methylguanine-DNA methyltransferase and human cancer chemotherapy.
Two kinds of human tumor cell strains having different activity of O6-methylguanine-DNA methyltransferase (O6-MT) were transplanted into nude mice. Mice were then injected intraperitoneally (i.p.) with the bifunctional agent 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride(ACNU). The tumors with low O6-MT activity were quickly suppressed or cured. This result suggests that some tumors, if determined to have low O6-MT activity, might be cured if the host is treated with ACNU. This observation may open a new approach to experimental cancer chemotherapy. Treatment with ACNU of experimental animals bearing HeLaMR tumors (which have low O6-MT activity and are Mer-), resulted in the regression of the tumors or their disappearance. In animals bearing HeLaS3 tumors (which have high O6-MT activity and are Mer+) the tumors were hyperplastic.
Wang
D W
DW
Department of Pathology, Academy of Military Medical Sciences, Beijing, PR China.
Zhang
Y P
YP
Li
J X
JX
Wang
X M
XM
Wang
B Z
BZ
Chen
Y N
YN
Wu
Y
Y
Yang
Y
Y
D000818:Animals; D002277:Carcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008780:Methyltransferases / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008854:Microscopy, Electron; D015376:Nimustine / Q000008:administration & dosage*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
D015376:Nimustine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase