The synergistic lethal interaction of Cis-diamminedichloroplatinum and natural nucleosides is related to increased DNA cross-links

B. Drewinko; M. A. Dipasquale; L. Y. Yang; B. Barlogie; J. M. Trujillo

doi:10.1016/S0009-2797(85)80116-2

The synergistic lethal interaction of Cis-diamminedichloroplatinum and natural nucleosides is related to increased DNA cross-links

B. Drewinko
, M. A. Dipasquale
, L. Y. Yang
, B. Barlogie
, J. M. Trujillo

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Human tumor cells were treated in vitro with combinations of cis- or trans-dichlodiammineplatinum (DDP) and natural nucleosides (thymidine, uridine, cytidine and adenosine). Effects were measured by inhibition of colony-formation (cell survival) and DNA alkaline elution (DNA cross-links). No increments in cell lethality or DNA cross-links were elicited by any combination of trans-DDP and nucleosides. In contrast, every combination of cis-DDP and nucleoside was eminently synergistic with 5- and 10-fold increases in cell lethality over the predicted sum of each agent alone. These increments in cell kill correlated linearly with increases in DNA crosslinks suggesting that the nucleosides interact with cis-DDP to enhance its cytotoxic crosslinking mode of action.

Original language	English
Pages (from-to)	1-12
Number of pages	12
Journal	Chemico-Biological Interactions
Volume	55
Issue number	C
DOIs	https://doi.org/10.1016/S0009-2797(85)80116-2
State	Published - 1985
Externally published	Yes

Keywords

Cisplatin
Cross-links
Cytotoxicity nucleosides
Synergism

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10.1016/S0009-2797(85)80116-2

Cite this

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title = "The synergistic lethal interaction of Cis-diamminedichloroplatinum and natural nucleosides is related to increased DNA cross-links",

abstract = "Human tumor cells were treated in vitro with combinations of cis- or trans-dichlodiammineplatinum (DDP) and natural nucleosides (thymidine, uridine, cytidine and adenosine). Effects were measured by inhibition of colony-formation (cell survival) and DNA alkaline elution (DNA cross-links). No increments in cell lethality or DNA cross-links were elicited by any combination of trans-DDP and nucleosides. In contrast, every combination of cis-DDP and nucleoside was eminently synergistic with 5- and 10-fold increases in cell lethality over the predicted sum of each agent alone. These increments in cell kill correlated linearly with increases in DNA crosslinks suggesting that the nucleosides interact with cis-DDP to enhance its cytotoxic crosslinking mode of action.",

keywords = "Cisplatin, Cross-links, Cytotoxicity nucleosides, Synergism",

author = "B. Drewinko and Dipasquale, \{M. A.\} and Yang, \{L. Y.\} and B. Barlogie and Trujillo, \{J. M.\}",

year = "1985",

doi = "10.1016/S0009-2797(85)80116-2",

language = "English",

volume = "55",

pages = "1--12",

journal = "Chemico-Biological Interactions",

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TY - JOUR

T1 - The synergistic lethal interaction of Cis-diamminedichloroplatinum and natural nucleosides is related to increased DNA cross-links

AU - Drewinko, B.

AU - Dipasquale, M. A.

AU - Yang, L. Y.

AU - Barlogie, B.

AU - Trujillo, J. M.

PY - 1985

Y1 - 1985

N2 - Human tumor cells were treated in vitro with combinations of cis- or trans-dichlodiammineplatinum (DDP) and natural nucleosides (thymidine, uridine, cytidine and adenosine). Effects were measured by inhibition of colony-formation (cell survival) and DNA alkaline elution (DNA cross-links). No increments in cell lethality or DNA cross-links were elicited by any combination of trans-DDP and nucleosides. In contrast, every combination of cis-DDP and nucleoside was eminently synergistic with 5- and 10-fold increases in cell lethality over the predicted sum of each agent alone. These increments in cell kill correlated linearly with increases in DNA crosslinks suggesting that the nucleosides interact with cis-DDP to enhance its cytotoxic crosslinking mode of action.

AB - Human tumor cells were treated in vitro with combinations of cis- or trans-dichlodiammineplatinum (DDP) and natural nucleosides (thymidine, uridine, cytidine and adenosine). Effects were measured by inhibition of colony-formation (cell survival) and DNA alkaline elution (DNA cross-links). No increments in cell lethality or DNA cross-links were elicited by any combination of trans-DDP and nucleosides. In contrast, every combination of cis-DDP and nucleoside was eminently synergistic with 5- and 10-fold increases in cell lethality over the predicted sum of each agent alone. These increments in cell kill correlated linearly with increases in DNA crosslinks suggesting that the nucleosides interact with cis-DDP to enhance its cytotoxic crosslinking mode of action.

KW - Cisplatin

KW - Cross-links

KW - Cytotoxicity nucleosides

KW - Synergism

UR - https://www.scopus.com/pages/publications/0022344197

U2 - 10.1016/S0009-2797(85)80116-2

DO - 10.1016/S0009-2797(85)80116-2

M3 - Article

C2 - 4064187

AN - SCOPUS:0022344197

SN - 0009-2797

VL - 55

SP - 1

EP - 12

JO - Chemico-Biological Interactions

JF - Chemico-Biological Interactions

IS - C

ER -

The synergistic lethal interaction of Cis-diamminedichloroplatinum and natural nucleosides is related to increased DNA cross-links

Abstract

Keywords

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