Temperature influences both cytotoxicity and DNA nicking efficiency of the antitumor distamycin analogue FCE24517.
The number of DNA single strand breaks generated by FCE24517 increases exponentially while covalent adducts linearly accumulate at a higher rate. Kinetics studies indicate that the rate of DNA fragmentation is temperature-dependent. The sites of DNA strand breaks do not change in the 30-65 degrees C range. The cytotoxic potency of FCE24517 is also affected by temperature, since a shift up of 6 degrees C during the 4 h exposure of human colon carcinoma cells raises the cytotoxic efficiency fivefold. These results are consistent with the hypothesis that the biological activity of this new drug relates to its electrophilic properties.
Montecucco
A
A
Istituto di Genetica Biochimica ed Evoluzionistica, CNR, Pavia, Italy.
Capolongo
L
L
Melegaro
G
G
Mondello
C
C
Ciarrocchi
G
G
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics; D000970:Antineoplastic Agents / Q000378:metabolism / Q000633:toxicity*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000187:drug effects; D004278:DNA, Superhelical / Q000187:drug effects; D004214:Distamycins / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D014411:Neoplastic Stem Cells; D009588:Nitrogen Mustard Compounds / Q000378:metabolism / Q000633:toxicity*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004277:DNA, Single-Stranded; D004278:DNA, Superhelical; D004214:Distamycins; D009588:Nitrogen Mustard Compounds; C066900:tallimustine