Effect of heat on the cytotoxicity and interaction with DNA of a series of platinum complexes

Mechanism of hyperthermic potentiation of cisplatin action in cisplatin-sensitive and -resistant tumour cells

“…Also, heat may have increased the reactivity of cDDP with DNA. In vitro incubation of plasmid DNA with cDDP revealed increased reaction rates at 42°C compared with 37°C (Herman et al, 1989), whereas the reaction of cDDP with salmon sperm DNA in solution showed no temperature dependency (Los et al, 1993). Both experiments, however, do not take into account the complex structure of DNA in the eukaryotic nucleus.…”

“…The mechanism(s) by which hyperthermia sensitizes cells to cDDP is (are) less clear. Altered platinum (Pt) accumulation, total Pt-DNA adduct and DNA cross-link formation and/or repair of DNA damage have been reported as a result of combined heat and cDDP treatments (Meyn et al, 1980;Wallner et al, 1986;Herman et al, 1988Herman et al, , 1989Herman et al, , 1990Mann et al, 1988;Mansouri et al, 1989;Eichholtz-Wirth and Hietel, 1990;Los et al, 1993;Takahashi et al, 1993;Ohno et al, 1994). However, the published data are rather contradictory, and in most papers only some of the abovementioned parameters were studied.…”

The influence of temperature on antiproliferative effects, cellular uptake and DNA platination of the clinically employed Pt(II)-drugs

“…At a first glance, cisplatin shows the greatest enhancement in cell killing with heat among platinum(II) complexes [25,28,31,32]. Increased drug accumulation by hyperthermia is one of the mechanisms involved in increased cisplatin toxicity and induced apoptosis in many human tumour types [29,35,36].…”

“…The combination of hyperthermia with some anticancer drugs has led to the overall enhancement of cytotoxicity. This effect has been attributed to: increased drug uptake, modification of its intracellular distribution, alteration of its metabolism, increased DNA lesion, and inhibition of DNA repair [20][21][22][23][24][25][26][27][28].…”

Cisplatin and platinum pharmacokinetics during hyperthermic isolated limb perfusion for human tumours of the extremities

“…With CDDP this can be of advantage as hyperthermia may enhance its cytoxicity (Fisher & Hahn, 1982;Hahn, 1979;Herman, 1983;Wallner et al, 1986;Alberts et al, 1980;Meyn et al, 1980). Enhanced blood flow, due to vasodilation (Hahn, 1979;Song et al, 1980), enhanced cellular drug uptake (Herman, 1983;Alberts et al, 1980), tissue extraction (Riviere et al, 1986), DNA cross-linking (Meyn et al, 1980;Herman et al, 1989) and decreased DNA repair (Wallner et al, 1986) are postulated to explain the phenomenon of hyperthermic potentiation. Some selectivity of treatment might hereby be introduced, because malignant cells have shown to be more sensitive to heat than normal cells (Herman, 1983;Herman et al, 1989;Giovanella et al, 1973;Giovanella et al, 1976;Kase & Hahn, 1975;Cavaliere et al, 1967).…”