| First Author | Sakumi K | Year | 1997 |
| Journal | Cancer Res | Volume | 57 |
| Issue | 12 | Pages | 2415-8 |
| PubMed ID | 9192819 | Mgi Jnum | J:41434 |
| Mgi Id | MGI:893912 | Citation | Sakumi K, et al. (1997) Methylnitrosourea-induced tumorigenesis in MGMT gene knockout mice. Cancer Res 57(12):2415-8 |
| abstractText | 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. |
