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Responses of Cycling and Noncycling Cells to 1,3-Bis(2-chloroethyl)-1-nitrosourea and to Bleomycin¹

Department of Radiology, Stanford University School of Medicine, Stanford, California 94305

The current literature contains conflicting data on the response of cycling and noncycling cells to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and to bleomycin (BLEO). Such data may be important for the design of multiple drug protocols for the treatment of solid cancers and we therefore reinvestigated these responses. After exposure to graded doses of BCNU, the survival curves of exponentially growing and plateau phase Chinese hamster cells (HA1) were quite similar, provided the agent was dissolved in isotonic buffer containing no protein. The responses of these cells to BCNU dissolved in media supplemented with serum were variable, depending upon the batch of serum and upon the experimental protocol. The results indicate that perhaps the reported far greater sensitivity to BCNU of noncycling cells is at least in part an artifact of the binding of the drug to serum components. No similar artifact was found for BLEO. Experiments involving sequential administration of BLEO and 5-fluorouracil to mice bearing a tissue culture-adapted mammary sarcoma (EMT-6) indicated that in vivo BLEO was at least as effective against noncycling tumor cells as against cycling tumor cells. However, repair of potentially lethal lesions strongly reduces the cell-killing ability of BLEO, a situation not found to be true for BCNU.

¹ Supported by USPHS Grants CA-04542 and CA-10372.

² Holder of a Dernham Senior Fellowship in Oncology from the California Division of the American Cancer Society.

Received 3/ 1/74. Accepted 5/23/74.