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Abstract
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.
Keywords
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Article info
Publication history
Accepted:
March 9,
1992
Received:
December 19,
1991
Identification
Copyright
© 1992 Published by Elsevier Inc.
