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Anticancer Res. 1999 May-Jun;19(3A):1729-35.

Overexpression of cDNA encoding FANCC, SPHAR, MPG, SNM1 or HA 3611 does not render CHO cells more resistant to DNA crosslinking agents.

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Division of Applied Toxicology, Institute of Toxicology, University of Mainz, Germany.


DNA crosslinking agents (DCA) are commonly used cytostatic drugs, whose efficiency in tumor therapy is limited due to the appearance of drug resistant tumor cells. In an effort to modulate the resistance of cells to DCA, we transfected into Chinese hamster cells various cDNAs whose loss of function was previously shown to render cells more sensitive to crosslinking agents. We show that overexpression of FANCC, SPHAR, MPG, SNM1 or HA 3611 (a human homologue of the yeast crosslink DNA repair gene SNM1) does not alter the level of resistance of CHO cells to clinically relevant DCA, such as mafosfamide, melphalan and mitomycin C. Therefore, DCA resistance frequently observed in tumor cells is not likely to be the result of up-regulation of either one of these genes, but a more complex phenomenon. Also, the data suggest that protection of normal cells from toxic side effects of DCA cannot easily be accomplished by transfer of either one of these genes.

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