CYTO-TOXIC EFFECTS AND BIOLOGICAL-ACTIVITY OF 2-AZA-8-GERMANSPIRO[4,5]-DECANE-2-PROPANAMINE-8,8-DIETHYL-N,N-DIMETHYLDICHLORIDE (NSC 192965 - SPIROGERMANIUM) INVITRO

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42 (7), 2852-2856
Abstract
Lethal and other biological effects of 2-aza-8-germanspiro[4,5]decane-2-propanamine-8,8-diethyl-N,N-dimethyl dichloride (NSC 192965; spirogermanium), representing a new chemical class of compound exhibiting antitumor activity, were studied in vitro. Survival curves for NIL 8 hamster cells were exponential with greater kill occurring with increasing drug concentrations and longer exposure times. Cytotoxicity was temperature dependent. Quiescent cultures were significantly less sensitive to spirogermanium than were logarithimically growing cells. These lethal effects showed no phase specificity. There was no evidence of progression delay through the cycle following spirogermanium treatment. When spirogermanium was tested against a range of human cell lines, the consistency of the values for the drug concentration required to reduce survival by 50% on the exponential part of the survival curve, derived from colony-forming assays, was most marked. The survival curves, characterized by an initial shoulder, were steep and exponential with measurements possible over only a narrow concentration range since complete cell lysis occurred at levels causing a >2-log kill. Cell membrane damage by spirogermanium, as judged by dye exclusion, was progressive with with time and increasing drug concentrations. Protein synthesis proved most susceptible to the drug. Spirogermanium concentrations cytotoxic to tumor cells were also toxic to cultured rat neurons, confirming the clinical neurological toxicity encountered. The precise mode of action of spirogermanium remains to be extablished, and these data further illustrate its apparent lack of specificity.