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Journal ArticleDOI

The anticancer agent adriamycin can be actively cytotoxic without entering cells

Thomas R. Triton, +1 more
- 16 Jul 1982 - 
- Vol. 217, Iss: 4556, pp 248-250
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TLDR
An agent whose principal target was previously thought to be DNA can exert its cytotoxic action solely by interaction at the cell surface by coupled to an insoluble agarose support.
Abstract
The antineoplastic agent adriamycin was coupled to an insoluble agarose support This material was actively cytotoxic to L1210 cells in culture under conditions in which no free adriamycin could enter the cell It is concluded that an agent whose principal target was previously thought to be DNA can exert its cytotoxic action solely by interaction at the cell surface

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Citations
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Journal ArticleDOI

A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin

TL;DR: The potential role of DNA synthesis inhibition, free radical formation and lipid peroxidation, DNA binding and alkylation, DNA cross-linking, interference with DNA strand separation and helicase activity, direct membrane effects, and the initiation of DNA damage via the inhibition of topoisomerase II in the interaction of these drugs with the tumor cell are addressed.
Journal ArticleDOI

Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II

TL;DR: In studies in vitro, mammalian DNA topoisomerase II mediates DNA damage by adriamycin and other related antitumor drugs, and has been shown to induce single- and double-strand breaks in DNA.
Journal ArticleDOI

Intercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II.

TL;DR: The agreement between the in vivo and in vitro studies suggests that mammalian DNA topoisomerase II is a drug target in vivo, and the cytotoxic action of epipodophyllotoxins may be analogous to the bactericidal action of nalidixic acid.
Journal ArticleDOI

The relevance of tumour pH to the treatment of malignant disease.

TL;DR: Low pH leads to decreased cell survival following treatment with hyperthermia, radiotherapy combined with hyperThermia, radiosensitizers and various chemotherapeutic agents, and low pH affords some protection against radiation and some drugs.
Journal ArticleDOI

Physiologically based pharmacokinetic modeling: Principles and applications

TL;DR: I was evaluated as a model organic anionic compound by characterizing the pharmacokinetics at three different doses and it was demonstrated that the biliary excretion of I depended on the amount present in the liver, and a saturable uptake process.
References
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Journal ArticleDOI

NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals

TL;DR: It is postulate that the formation of the "site-specific free radical/ intermediate is central to the cytotoxic action of these antibiotics.
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The incorporation of 3H-cytosine arabinoside and its effect on murine leukemic cells (L5178Y).

TL;DR: Murine leukemic cells, L5178Y, inhibited by a low level of cytosine arabino-side for 6 hr could be rescued by deoxycytidine, and the incorporation into RNA could be correlated with irreversible inhibition of cell reproduction.
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Adriamycin: a proposal on the specificity of drug action.

TL;DR: Evidence exists which indicates that certain neoplastic cells may contain cardiolipin in their plasma membrane and thus present a different surface to the drug than a non-malignant cell, which may be indicative of specificity in the cytotoxic action of adriamycin on tumors.
Journal ArticleDOI

Adriamycin-induced changes in the surface membrane of sarcoma 180 ascites cells

TL;DR: The results indicate that adriamycin can induce changes in the surface membrane of Sarcoma 180 cells within a brief period of exposure to a low but cytotoxic level of this agent.
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