Assessment of the inhibitory effects of different radiation qualities or chemotherapeutic agents on a human melanoma cell line.
The correlation between time dependent viabilities, after applying two radiation qualities and two alkylating agents on HTB140 melanoma cells, has been studied. Irradiations were performed with gamma-rays and 62 MeV protons, close to the Bragg peak maximum, delivering doses of 8-24 Gy. Treatments with fotemustine (FM) and dacarbazine (DTIC) were carried out with concentrations of 0.05-2mM. High radio-resistance of HTB140 cells revealed by a clonogenic assay was confirmed by microtetrasolium and sulforhodamine B, through the surviving fraction at 2 Gy (SF2), being 0.961-0.956 for gamma-rays and 0.931-0.887 for protons. A better efficiency of protons was illustrated by relative biological effectiveness at 2 Gy (RBE), ranging from 1.69 to 1.89. A kinetic study of concentration dependent cytotoxicity indicated that the best effect of the drugs, estimated as the concentration that produces 50% of growth inhibition (IC(50)), was obtained at 48 h, having values of 76 microM for DTIC and 145 microM for FM. The cytostatic ability of the drugs pointed out that the presence of DTIC at 24h, compared to FM, was insufficient to produce an effect. Protons and FM demonstrated their pro apoptotic capacity. Cross-resistance between treatments applied to the HTB140 cells was observed, protons being the most efficient, while DTIC, FM and gamma-rays demonstrated a lower level of cell inactivation.
Laboratory of Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, Mihajla Petrovica Alasa 12-14, 11001 Belgrade, Serbia. aristic@vin.bg.ac.yu
Aleksandra M
AM
Ristić-Fira
Ivan M
IM
Petrović
Lela B
LB
Korićanac
Lucia M
LM
Valastro
Giuseppe
G
Privitera
Giacomo
G
Cuttone
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008545:Melanoma / Q000473:pathology* / Q000503:physiopathology*; D011829:Radiation Dosage
D000970:Antineoplastic Agents