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. 1985 Aug;52(2):251–258. doi: 10.1038/bjc.1985.185

The effects of pretreatment of human tumour cells with MNNG on the DNA crosslinking and cytotoxicity of mitozolomide.

N W Gibson, L C Erickson
PMCID: PMC1977104  PMID: 4027167

Abstract

Mitozolomide and its decomposition product MCTIC were found to be more cytotoxic to BE colon carcinoma cells in vitro than to HT-29 cells, another colon carcinoma cell line. In addition mitozolomide and MCTIC induced DNA interstrand crosslinks in the BE but not the HT-29 cell line. BE cells are deficient in the repair of O6-methylguanine lesions and are designated Mer-, whereas, HT-29 cells are proficient in this repair process and are designated Mer+. Thus DNA interstrand crosslinking produced by mitozolomide and MCTIC appears to correlate with the Mer phenotype. Pretreatment of HT-29 cells (Mer+) with the DNA methylating agent MNNG allows mitozolomide or MCTIC to produce DNA interstrand crosslinks. HT-29 cells also become more sensitive to the cell killing of mitozolomide and MCTIC with MNNG pretreatment. Pretreatment of Mer- cells (BE) had little effect on either cell killing or DNA crosslinking levels induced by mitozolomide or MCTIC. DNA interstrand crosslinking induced by mitozolomide and MCTIC is probably a consequence of an initial alkylation at the O6-position of guanine followed by a delayed reaction with the opposite DNA strand.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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