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Inhibitory Effect of Adenosine Dialdehyde on in Situ Murine Neuroblastoma Growth¹

Divisions of Clinical Pharmacology and Pediatric Oncology, Departments of Pediatrics [B. B., B. L. M.] Pharmacology [B. L. M.], and Biochemistry [H. P. C. H.], Variety Club Children's Hospital, University of Minnesota, Minneapolis, Minnesota 55455

The effect of adenosine dialdehyde (AD) on in situ tumor growth and host survival was evaluated in the C1300 murine neuroblastoma tumor model prepared by implantation of murine neuroblastoma cells into A/J mice. AD was administered s.c. by one of the following treatment regimens: regimen A, single daily dose for 5 days; regimen B, minipump infusion for 7 days; regimen C, minipump infusion for 14 days; regimen D, minipump infusion for two 7-day periods interspersed by a 7-day drug free interval. AD doses of 1.5 to 2.5 mg/kg/day infused over a 7-day period (regimen B) significantly increased the mean life span of tumor bearing mice from 20.9 ± 1.2 days (mean ± 2 SEM) in diluent treated controls to 35.3 ± 2.1 days in AD treated animals (mean increase ± 2 SEM: 69 ± 10%; P < 0.0001). This treatment regimen also produced a 56 ± 13% decrease in tumor diameter (P < 0.0001). Administration of AD for two 7-day infusion periods, interspersed by a 7-day drug free interval (regimen D), increased mean life span 80% (controls, 21.3 ± 4.4 days; AD treated 38.4 ± 5.6 days; P < 0.0005). Hematopoietic toxicity was not observed when doses between 2 and 3 mg/kg/day of AD were infused for 7 days (regimen B). These data suggest that steady state infusions of AD can significantly suppress murine neuroblastoma tumor growth with little systemic toxicity. In contrast, single daily injections of AD were ineffective and toxic to the tumor bearing host.

¹ This research was supported by USPHS Grant NS17194, The Viking's Children's Fund, and The Children's Cancer Research Fund of the University of Minnesota.

² To whom requests for reprints should be addressed, at Division of Clinical Pharmacology, Departments of Pediatrics and Pharmacology, Box 87 UMHC, University of Minnesota Health Sciences Center, Minneapolis, MN 55455.

Received 1/14/88. Revised 5/16/88. Accepted 7/26/88.