Identification of nitrosourea-resistant human rhabdomyosarcomas by in situ immunostaining of O6-methylguanine-DNA methyltransferase.
AuthorsBrent, T P
Von Wronski, M A
Edwards, C C
Margison, Geoffrey P
Rafferty, Joseph A
Pegram, C N
Bigner, D D
AffiliationDepartment of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, TN.
MetadataShow full item record
AbstractCellular levels of O6-methylguanine-DNA methyltransferase (MGMT) correlate strongly with cellular resistance to carcinogenic and chemotherapeutic agents that produce adducts at the O6-position of guanine in DNA. Although biochemical and molecular assays can indicate the average MGMT content of tissues or tumors, they cannot distinguish mixed populations of cells, such as those that exist in tumor biopsy samples. We have determined MGMT at the cellular level in a panel of pediatric rhabdomyosarcoma xenografts by in situ immunostaining with a human MGMT-specific antibody employing a very sensitive procedure that involves biotin-avidin coupled horseradish peroxidase with silver-enhanced diaminobenzidine-nickel staining. Two xenograft tumor lines known to be MGMT-deficient were not stained, whereas the nuclei in three MGMT-expressing lines were clearly stained. This is the first demonstration of an in situ procedure that discriminates drug-sensitive MGMT-deficient tumors from drug-resistant MGMT expressing tumors. This procedure should prove useful, therefore, for predicting the susceptibility of tissues and tumors to O6-guanine alkylating agents.
CitationIdentification of nitrosourea-resistant human rhabdomyosarcomas by in situ immunostaining of O6-methylguanine-DNA methyltransferase. 1993, 5 (2):83-6 Oncol. Res.
- Cytosine methylation and suppression of O6-methylguanine-DNA methyltransferase expression in human rhabdomyosarcoma cell lines and xenografts.
- Authors: von Wronski MA, Harris LC, Tano K, Mitra S, Bigner DD, Brent TP
- Issue date: 1992
- Role of O6-methylguanine-DNA methyltransferase in the resistance of pancreatic tumors to DNA alkylating agents.
- Authors: Kokkinakis DM, Ahmed MM, Delgado R, Fruitwala MM, Mohiuddin M, Albores-Saavedra J
- Issue date: 1997 Dec 1
- Treatment of human brain tumor xenografts with O6-benzyl-2'-deoxyguanosine and BCNU.
- Authors: Schold SC Jr, Kokkinakis DM, Rudy JL, Moschel RC, Pegg AE
- Issue date: 1996 May 1
- Expression of O6-methylguanine-DNA methyltransferase and chloroethylnitrosourea resistance of human brain tumors.
- Authors: Nagane M, Asai A, Shibui S, Nomura K, Matsutani M, Kuchino Y
- Issue date: 1992 Jun
- In situ detection of O6-methylguanine-DNA methyltransferase messenger RNA in paraffin-embedded human astrocytic tumor tissues by nested in situ RT-PCR is useful in predicting chemotherapy-resistance of tumors.
- Authors: Ohe N, Saio M, Kijima M, Tamakawa N, Suwa T, Kojima Y, Yano H, Kaku Y, Iwama T, Shinoda J, Sakai N, Takami T
- Issue date: 2003 Mar