Tris (1-aziridinyl) phosphine oxide (TEPA) and tris (1-aziridinyl) phosphine sulfide (thio-TEPA) induced base pair mutations in the Ames mutagenic assay. Thio-TEPA required metabolic activation while TEPA was active without metabolic activation. Growth of a human vaginal carcinoma (A431), a human breast carcinoma (MDAMB-231), and a human cervical carcinoma (HeLa) were inhibited in soft agar in vitro at concentrations which induced mutagenesis in the Ames Assay. A fourth line, JEG choriocarcinoma, was sensitive to the antigrowth properties of both drugs at concentrations below that which induced mutagenesis. These data suggest that as more antineoplastic agents become available, and as mean survival times increase, knowledge of the relative in vitro sensitivity of a patient's neoplasm to a specific antineoplastic drug (i.e., dose required for growth inhibition) as a function of its mutagenic index might be useful for prediction of clinical remission, as well as the risk of secondary neoplasm induction.
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Abbreviations
- TEPA:
-
tris (1-aziridinyl) phosphine oxide
- thio-TEPA:
-
tris (1-aziridinyl) phosphine sulfide
- MEM:
-
Minimal Essential Media
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This study was supported by PHS grant No. CA 30321 awarded by the National Cancer Institute (DHHS).
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Breau, A.P., Field, L. & Mitchell, W.M. Thiono compounds. 4. In vitro mutagenic and antineoplastic activity of TEPA and thio-TEPA. Cell Biol Toxicol 1, 21–30 (1984). https://doi.org/10.1007/BF00125562
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DOI: https://doi.org/10.1007/BF00125562