Localization and therapeutic potential of tritiated tetracycline in rodent tumors
Davis, R.C.; Wood, P.; Mendelsohn, M.L.
Cancer Research 37(12): 4539-4545
1977
ISSN/ISBN: 0008-5472 PMID: 922738 Document Number: 118692
The reputed localization of tetracycline in human and animal tumors suggested that chemically stable, high-specific-activity 3H-tetracycline (TTC) might have antineoplastic therapeutic potential. Direct therapeutic effects were tested in 2 transplanted tumor lines in rats, and the localizing properties of TTC were measured in 30 transplanted tumor lines in rats and mice and 23 spontaneous mammary tumors in rats. While a significant reduction in the growth rates of transplanted tumors could be obtained through the administration of heavy doses of TTC, similar reductions were observed in the growth rates of tumors in animals receiving unlabeled tetracycline. In the localization studies the concentrations of TTC in normal tissues and tumors were compared and correlated with corresponding concentrations of [14C]-thymidine, a measure of proliferative activity. Significantly greater binding of TTC over normal tissue occurred only in areas that failed to incorporate [14C]thymidine. Rapidly proliferating areas of tumors, as measured by [14C]thymidine incorporation, bound tetracycline in concentrations similar to muscle and significantly lower than kidney. The lack of localization in viable tumor and the absence of a 3H effect in treated tumors argues strongly against the therapeutic value of TTC at least to the extent that the results on this broad spectrum of tumors can be generalized.