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    Relative mutagenicity of antineoplastic drugs and other alkylating agents in V79 Chinese hamster cells, independence of cytotoxic and mutagenic responses.

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    Authors
    Suter, W
    Brennand, J
    McMillan, S
    Fox, Margaret
    Affiliation
    Paterson Laboratories, Christie Hospital and Holt Radium Institute, Withington, Manchester M20 9BX Great Britain
    Issue Date
    1980-11
    
    Metadata
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    Abstract
    The mutagenic and cytotoxic effects of 4 antineoplastic drugs, vinblastine, vincristine, adriamycin and nitrogen mustard and of several monofunctional alkylating agents have been assayed in V79 Chinese hamster cells. Vincristine, vinblastine and nitrogen mustard did not significantly increase the frequency of TGRHGPRT- mutants but were were all highly cytotoxic. Adriamycin and the monofunctional alkylating agents were all significantly mutagenic even at the lowest doses tested (approx. 70% survival level). Induced mutant frequency increased linearly with increasing dose whereas dose-response curves for cytotoxicity for these effective mutagens invariably showed a shoulder followed by an exponential decline. At equitoxic doses the relative mutagenic effectiveness was MNU > ENU > EMS > MNNG > MMS greater than or equal to DMS. MNU was approx. 20 times more effective than MMS and DMS. Measurement of the total amount of alkylation and the relative amounts of reaction with individual DNA bases at approx. equitoxic doses of MNU and DMS indicated a significantly higher O6/N7 ratio after MNU (0.15) than after DMS (0.005). However, approx. equal numbers of mutants/10(5) cells/microM O6-Meguanine were induced by these 2 agents. These results support previous conclusions, that mutagenic and cytotoxic responses are independent in V79 cells.
    Citation
    Relative mutagenicity of antineoplastic drugs and other alkylating agents in V79 Chinese hamster cells, independence of cytotoxic and mutagenic responses. 1980, 73 (1):171-81 Mutat. Res.
    Journal
    Mutation Research
    URI
    http://hdl.handle.net/10541/134869
    PubMed ID
    6265771
    Type
    Article
    Language
    en
    ISSN
    0027-5107
    Collections
    All Paterson Institute for Cancer Research

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