This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tofilon, P. J. Articles by Milas, L. Search for Related Content PubMed PubMed Citation Articles by Tofilon, P. J. Articles by Milas, L.

Prediction of in Vivo Tumor Response to Chemotherapeutic Agents by the in Vitro Sister Chromatid Exchange Assay¹

Department of Experimental Radiotherapy [P. J. T., I. B., L. M.], The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, Houston, Texas 77030

The ability of the in vitro sister chromatid exchange (SCE) assay to predict in vivo tumor drug sensitivity was investigated using a spontaneous hepatocarcinoma in C3Hf/Kam mice and 3 chemotherapeutic agents: melphalan; cis-platinum; and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). For hepatocarcinoma cells grown in monolayer culture, melphalan was the most efficient at inducing SCEs, and BCNU, the least. cis-Platinum induced a range in SCEs that overlapped those of BCNU and melphalan, suggesting that hepatocarcinoma is not a homogeneous population with intermediate sensitivity, but is a mixture of cis-platinum-sensitive and -resistant cells. According to in vitro cell survival curves, hepatocarcinoma was most sensitive to melphalan, less sensitive to cis-platinum, and essentially resistant to BCNU. The relative antineoplastic effects of melphalan, cis-platinum, and BCNU in vivo were compared by the response of artificial and spontaneous pulmonary metastases and solid tumors to these agents. For artificial metastases, there was a dose-dependent decrease in the number of lung nodules in mice treated with melphalan or cis-platinum, with melphalan being the more effective. BCNU had no effect. Spontaneous pulmonary metastases generated from hepatocarcinoma leg tumors were reduced in those mice treated with melphalan, unaffected by cis-platinum, and increased by BCNU. In hepatocarcinoma leg tumors (5 to 6 mm in diameter), melphalan induced the longest growth delay, and BCNU the least. Therefore, the relative effects produced by these three drugs in vivo were the same as predicted by SCE induction in vitro. The SCE assay may thus have potential clinical application.

¹ This investigation was supported in part by NIH Research Grants CA-39465 and CA-06294. Animals used in this study were maintained in facilities approved by the American Association for Accreditation of Laboratory Animal Care, and in accordance with current regulations and standards of the United States Department of Agriculture and Department of Health and Human Services, NIH.

² To whom requests for reprints should be addressed, at Department of Experimental Radiotherapy, Mail Box 66, M. D. Anderson Hospital, 6723 Bertner Ave., Houston, TX 77030.

³ On leave of absence from University of Zagreb, Faculty of Natural Sciences and Mathematics, Department of Animal Physiology, Zagreb, Yugoslavia.

Received 10/ 9/84. Revised 12/11/84. Accepted 1/28/85.

This article has been cited by other articles:

				T. Lialiaris, E. Lyratzopoulos, F. Papachristou, M. Simopoulou, C. Mourelatos, and N. Nikolettos Supplementation of melatonin protects human lymphocytes in vitro from the genotoxic activity of melphalan Mutagenesis, September 1, 2008; 23(5): 347 - 354. [Abstract] [Full Text] [PDF]

				A.A. Pantazaki and Th.S. Lialiaris A combined biochemical and cytogenetic study of thioridazine-induced damage to nucleic acids Mutagenesis, March 1, 1999; 14(2): 243 - 248. [Abstract] [Full Text] [PDF]