Methylnitrosourea-induced tumorigenesis in MGMT gene knockout mice.
Cancer Res
; 57(12): 2415-8, 1997 Jun 15.
Article
in En
| MEDLINE
| ID: mdl-9192819
ABSTRACT
Gene targeting was used to obtain mice defective in the MGMT gene, encoding O6-methylguanine-DNA methyltransferase [Tsuzuki et al., Carcinogenesis (Lond.), 17 1215-1220, 1996]. These MGMT-/- mice were most sensitive to the alkylating carcinogen, methylnitrosourea; when varied doses of methylnitrosourea were administered to 6-week-old mice and survivals at the 30th day were determined, LD50s of MGMT-/- and MGMT+/+ mice were 20 and 240 mg/kg of body weight, respectively. MGMT+/- mice were as resistant as MGMT+/+ mice, but some difference in survival time was noted when the two genotypes of mice were exposed to a relatively high dose of methylnitrosourea. A large number of thymic lymphomas, as well as lung adenomas, occurred in MGMT-/- mice exposed to methylnitrosourea at a dose of 2.5 mg/kg of body weight. In case of exposure to the same dose of drug, no or few tumors occurred in the MGMT+/+ and MGMT+/- mice. It appears that the DNA repair methyltransferase protein protected these mice from methylnitrosourea-induced tumorigenesis.
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Database:
MEDLINE
Main subject:
Thymus Neoplasms
/
Carcinogens
/
Lung Neoplasms
/
Methylnitrosourea
/
Methyltransferases
Limits:
Animals
Language:
En
Year:
1997
Type:
Article