Open AccessProtection against Malignant Progression of Spontaneously Developing Liver Tumors in Transgenic Mice Expressing O 6 ‐Methylguanine‐DNA Methyltransferase
Author(s) -
Qin Xiusheng,
Zhang Shaomin,
Matsukuma Shoichi,
Zarkovic Mirjana,
Shimizu Seiichiro,
Ishikawa Takatoshi,
Nakatsuru Yoko
Publication year - 2000
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2000.tb00888.x
Subject(s) - carcinogenesis , genetically modified mouse , methyltransferase , transgene , biology , cancer research , oncogene , o 6 methylguanine dna methyltransferase , dna repair , mutation , dna damage , tumor progression , microbiology and biotechnology , gene , dna , genetics , cell cycle , methylation
To study the effect of O 6 ‐methylguanine‐DNA methyltransferase (MGMT) on carcinogenesis, we have previously generated MGMT transgenic mice overexpressing the bacterial MGMT gene, ada , and demonstrated that high MGMT levels in the liver suppress induction of liver tumors after treatment with an alkylating hepatocarcinogen. To examine the effects of life‐long elevation of MGMT activity on mouse spontaneous liver tumor development, ada‐transgenic and control nontransgenic mice were compared. We also examined mutations at codon 61 of the H‐ras oncogene, reported as a hot spot in mouse liver tumors, using a direct DNA sequencing method. The results revealed no significant difference in tumor incidence or mutation spectrum, but interestingly, ada‐transgenic mice were found to have fewer malignant tumors and survived longer, indicating a possible protective role of MGMT against malignant conversion.