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Thiono compounds. 4. In vitro mutagenic and antineoplastic activity of TEPA and thio-TEPA (1984)

Breau, Alan P. ; Field, Lamar ; Mitchell, William M.

Springer

Cell biology and toxicology 1 (1984), S. 21-30

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ISSN: 1573-6822

Keywords: tris (1-aziridinyl) phosphate oxide ; tris (1-aziridinyl) phosphate sulfide ; base pair mutations ; Ames mutagenic assay (Salmonella assay) ; human breast carcinoma ; human cervical carcinoma ; human vaginal carcinoma

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Medicine

Notes: 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.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00125562

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The correlation of plasma membrane microvilli and intracellular cyclic AMP content in a rat epitheloid kidney cell line (1976)

Carley, William W. ; Moses, Harold L. ; Mitchell, William M.

New York, N.Y. : Wiley-Blackwell

Journal of Supramolecular Structure 5 (1976), S. 309-316

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ISSN: 0091-7419

Keywords: temperature sensitive mutants ; plasma membrane microvilli ; cyclic AMP ; scanning electron microscopy ; cell synchrony ; neoplastic ; epitheloid cells ; Kirsten murine ; cell tissue culture ; Life Sciences ; Molecular Cell Biology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Chemistry and Pharmacology , Medicine

Notes: Modulation of the intracellular concentration of cyclic AMP has been associated with a regulatory role in cell division, cell morphology, and physical properties of the plasma membrane. Untransformed rat kidney cells in culture exhibit epitheloid morphology, high intracellular cyclic AMP levels, and contact inhibition of growth. Untransformed rat kidney cells transformed with the Kirsten murine sarcoma virus exhibit a low cyclic AMP content, rapid growth rate, and a loss of contact inhibition. Scanning electron microscopy reveals a distinctive difference in the surface structure of the two cell types during G1 of the cell cycle. The surface of the transformed cell is covered with microvilli while its untransformed counterpart is devoid of microvilli. The presence of microvilli can be controlled as a function of temperature by two temperature-sensitive mutants of the Kirsten sarcoma virus (ts6t6 and ts371 cl 5). In the ts6t6 mutant, growth at 32°C results in a low cyclic AMP content and the presence of microvilli, while growth at 39°C results in a high cyclic AMP content and a decrease in microvilli. The oposite effect is seen with the ts371 cl 5 mutant. Correlation of cyclic AMP content with the presence of microvilli suggests that this surface phenomenon is a function of cyclic AMP concentration.

Additional Material: 4 Ill.