Temperature induced interstrand crosslinks in cisplatin-DNA adducts detected by electrophoresis and UV spectrophotometer.
Thermal melting profiles of DNA samples complexed with the anti-tumor drug cisplatin exhibit significant hypochromicity at pre-melting temperatures while a reduction in total hyperchromicity is observed in the melting region. Densitometric analysis of agarose gel electrophoresis pattern of DNA-cisplatin adducts heated to different temperatures in the pre-melting region and frozen in their conformations reveals a gradual retardation of mobility as the temperature increases. We attribute these results to a temperature induced transition in the mode of binding of cisplatin to DNA from an initial intrastrand monofunctional binding to bifunctional interstrand crosslink formation which results in gradual bending of the helix.
Narasimhan
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Department of Chemistry and Physics, Skidmore College, Saratoga Springs, NY 12866, USA.
Malboueuf
B
B
Hodil
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SE
D000970:Antineoplastic Agents / Q000737:chemistry*; D002945:Cisplatin / Q000737:chemistry*; D018736:DNA Adducts / Q000737:chemistry*; D004587:Electrophoresis, Agar Gel; D006147:Guanine / Q000737:chemistry; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009695:Nucleic Acid Renaturation; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
D000970:Antineoplastic Agents; D018736:DNA Adducts; D006147:Guanine; D002945:Cisplatin