The effect of hypoxia on cytotoxicity, accumulation and DNA binding of cisplatin in Chinese hamster ovary cells.
The literature contains conflicting evidence regarding the hypoxic toxicity of cisplatin. We have found that in Chinese hamster ovary cells, cisplatin was up to 2.6 times more effective at reducing survival to 2% in hypoxic, compared with aerobic cells. Furthermore, using atomic absorption spectroscopy, it was determined that cells treated in hypoxia showed consistently higher accumulation (up to 1.5 times) and DNA binding (up to 1.7 times) than aerobic cells. Hypoxic cells also showed greater toxicity per platinum-DNA adduct than those treated in air, suggesting that increased binding of the drug, alone, cannot account for its increased hypoxic cytotoxicity. We suggest that the hypoxia selectivity of cisplatin involves several different mechanisms and possible explanations for these results are discussed.
Matthews
J B
JB
BC Cancer Research Centre, Vancouver, Canada.
Adomat
H
H
Skov
K A
KA
D000332:Aerobiosis; D000818:Animals; D016466:CHO Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology*; D002945:Cisplatin / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D006224:Cricetinae; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage; D010100:Oxygen / Q000502:physiology
D004247:DNA; D002945:Cisplatin; D010100:Oxygen