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Science 23 March 1990:
Vol. 247. no. 4949, pp. 1457 - 1461
DOI: 10.1126/science.2108497
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Articles

Science, Vol 247, Issue 4949, 1457-1461
Copyright © 1990 by American Association for the Advancement of Science

articles

Tumor resistance to alkylating agents conferred by mechanisms operative only in vivo

BA Teicher, TS Herman, SA Holden, YY Wang, MR Pfeffer, JW Crawford, and E Frei 3rd

Dana-Farber Cancer Institute, Boston, MA 02115.

EMT-6 murine mammary tumors were made resistant to cis-diamminedichloroplatinum (II) (CDDP), carboplatin, cyclophosphamide (CTX), or thiotepa in vivo by treatment of tumor-bearing animals with the drug during a 6-month period. In spite of high levels of in vivo resistance, no significant resistance was observed when the cells from these tumors were exposed to the drugs in vitro. The pharmacokinetics of CDDP and CTX were altered in animals bearing the respective resistant tumors. The resistance of all tumor lines except for the EMT-6/thiotepa decreased during 3 to 6 months in vivo passage in the absence of drugs. These results indicate that very high levels of resistance to anticancer drugs can develop through mechanisms that are expressed only in vivo.


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