Research Article| Volume 4, ISSUE 1, P6-10, July 1992

O6-Alkylguanine-DNA alkyltransferase activity in human malignant melanoma

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      O6-alkylguanine has been known to be the major lesion in DNA for the cytotoxicity of alkylating agents and it is repaired by O6-Alkylguanine-DNA alkyltransferase (O6-AGT). To examine the relation of O6-AGT to the clinical characteristics in malignant melanoma (MM), O6-AGT activity in 13 human MM tissues was measured. The activity in tumor tissues varied widely from 0 to 0.11 pmol/mg protein. The activity in normal skin tissues was lower and less variable than in the tumors. The activity was not related to the tumor size or clinical stage of melanomas, but it was higher in tumors after chemotherapy with alkylating agents than in those without chemotherapy. In metastatic tissues, in primary tumors of the patients with metastases and in tumors of the patients with bad prognosis, the activity was also high. Two of the tumors, having the highest O6-AGT activity, were both transplantable to nude mice. These results suggest two possibilities; melanomas exposed to the alkylating agents may change to have high O6-AGT activity, followed by the resistance to such agents, or O6-AGT in melanomas may be originally diverse. O6-AGT activity in the tumour tissue may represent the effect of alkylating agents and can be used in selecting the methods of therapy.


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        • Mackie RM
        4th Edn. Skin Cancer. Martin Dunitz Ltd, London1989: 178-201
        • Moriwaki SI
        • Yagi T
        • Nishigori C
        • Imamura S
        • Takebe H
        Analysis of N-methyl-N-nitrosourea-induced mutations in a shuttle vector plasmid propagated in mouse O6-methylguanine-DNA methyltransferase-deficient cells in comparison with proficient cells.
        Cancer Res. 1991; 51: 6219-6223
        • Pegg AE
        Mammalian O6-alkylguanine-DNA alkyltransferase: regulation and importance in response to alkylating carcinogenic and therapeutic agents.
        Cancer Res. 1990; 50: 6119-6129
        • Tsujimura T
        DNA damage produced by alkylating agents and their repair in human tumor cell strains.
        Med J Osaka Univ. 1987; 39: 195-209
        • Scudiero DA
        • Meyer SA
        • Clatterbuck BE
        • Mattern MR
        • Ziolkowski CHJ
        • Day III, RS
        Relationship of DNA repair phenotype of human fibroblast and tumor strains of killing by N-methyl-N′-nitroso-nitrosoguanidine.
        Cancer Res. 1984; 44: 961-969
        • Maynard K
        • Parsons PG
        • Cerny T
        • Margison GP
        Relationships among cell survival, O6-alkylguanine-DNA alkyltransferase activity, and reactivation of methylated adenovirus 5 and herpes simplex virus type 1 in human melanoma cell lines.
        Cancer Res. 1989; 49: 4813-4822
        • Gerson SL
        • Mitter K
        • Berger NA
        O6-Alkylguanine-DNA alkyltransferase activity in human myeloid cells.
        J Clin Invest. 1986; 76: 2106-2114
        • Gerson SL
        • Trey JE
        • Mitter K
        • Berger AN
        Comparison of O6-alkylguanine-DNA alkyltransferase activity based on cellular DNA content in human rat and mouse tissues.
        Carcinogenesis. 1986; 7: 745-749
        • Myrnes B
        • Norstrand K
        • Giercksky KE
        • Sjunneskog C
        • Krokan H
        A simplified assay for O6-methylguanine-DNA methyltransferase activity and its application to human neoplastic and nonneoplastic tissues.
        Carcinogenesis. 1984; 5: 1061-1064
        • Myrnes B
        • Giercksky KE
        • Krokan H
        Interindividual variation in the activity of O6-methylguanine-DNA methyltransferase and uracil-DNA glycosylase in human organs.
        Carcinogenesis. 1983; 4: 1565-1568
        • Frosina G
        • Rossi O
        • Arena G
        • Gentile SL
        • Bruzzone E
        • Abbondando A
        O6-Alkylguanine-DNA alkyltransferase activity in human brain tumors.
        Cancer Lett. 1990; 55: 153-158
        • Yarosh DB
        • Rice M
        • Day III, RS
        • Foote RS
        • Mitra S
        O6-Methylguanine-DNA methyltransferase in human cells.
        Mutat Res. 1984; 131: 27-36
        • Nishigori C
        • Moriwaki SI
        • Yagi T
        • Takebe H
        Altered O6-alkylguanine-DNA alkyltransferase activity in cell strains originating from mouse skin tumors induced by UV irradiation.
        Cancer Res. 1991; 51: 2425-2429
        • UICC
        Melanoma of skin.
        in: TNM Classification of Malignant Tumors. 4th Edn. Springer-Verlag, Berlin, Heiderberg, New York, London, Paris, Tokyo1987: 89-91
        • Hayakawa H
        • Koike G
        • Sekiguchi M
        Expression and cloning of complementary DNA for a human enzyme that repairs O6-methylguanine in DNA.
        J Mol Biol. 1990; 213: 739-747
        • Rydberg B
        • Hall J
        • Karran P
        Active site amino acid sequence of the bovine O6-methylguanine-DNA methyltransferase.
        Nucleic Acids Res. 1990; 18: 17-21
        • Tano K
        • Shiota S
        • Collier J
        • Foote RS
        • Mitra S
        Isolation and structural characterization of a cDNA clone encoding the human repair protein for O6-alkylguanine.
        in: 4th edn. Proc Natl Acad Sci USA. 87. 1990: 686-690
        • Clark Jr, WH
        • From L
        • Bernardino EA
        • Mihm MC
        The histogenesis and biologic behavior of primary human malignant melanomas of the skin.
        Cancer Res. 1969; 29: 705-726
        • Reed RJ
        4th edn. New Concepts in Surgical Pathology of the Skin. Wiley, New York1976: 89-90