Combination effects of cis-dichlorodiammineplatinum with selected metahalones, pyrimidine sulfoxides and pyrimidine sulfones on human NHIK 3025 cells in vitro.
Synergistic cell inactivating effects were displayed when human NHIK 3025 cells cultivated in vitro were treated with cis-dichlorodiammineplatinum(II) (cis-DDP) in simultaneous combination with selected metahalones, pyrimidine sulfoxides and sulfones. Cell inactivation was measured as the percentage of single cells surviving and able to give rise to macroscopic colonies following drug treatment. Selection of compounds was made according to the presence and position of certain structural groups. For 5-halo-pyrimidin-2-ones (the metahalones), a propargyl substituent attached to the pyrimidine ring at the 1-position resulted in compounds causing potentiation of cis-DDP-induced cell inactivation. An iodo or trifluoromethyl substituent at the 5-position led to a reduction in cis-DDP + metahalone synergism respective to a 5-chloro substituent. Cell survival following 1 h treatment with the metahalones alone was always near 100%. The cell inactivating effect of pyrimidine sulfoxides and sulfones alone and in simultaneous combination with cis-DDP was also investigated. Treatment of human cells with pyrimidine sulfoxides and sulfones alone resulted in reduced cell survival relative to the metahalones. When tested in combination with cis-DDP, pyrimidine sulfoxides and sulfones containing a propargyl moiety bound at the sulfur atom were found to potentiate the cell inactivating effect of cis-DDP. Other substituents induced only minor effects.
Dornish
J M
JM
Department of Tissue Culture, Norwegian Radium Hospital, Oslo.
Undheim
K
K
Pettersen
E O
EO
Oftebro
R
R
Laland
S G
SG
D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D011743:Pyrimidines / Q000494:pharmacology*; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000633:toxicity; D013450:Sulfones; D013454:Sulfoxides; D014407:Tumor Cells, Cultured
D011743:Pyrimidines; D011744:Pyrimidinones; D013450:Sulfones; D013454:Sulfoxides; C019002:metahalones; D002945:Cisplatin