PHARMACO-BIOCHEMICAL STUDIES ON CYTOTOXIC POLYOL DERIVATES .I. EFFECTS OF 1-6-DIBROMO-1-6-DIDEOXY-DULCITOL ON SENSITIVE, RESISTANT AND REFRACTOR TUMOURS

1-6-dibromo-1-6-dideoxy-dulcitol (DBD) has a curative effect on the Yoshida tumour. On the other hand, the same drug proved to be completely ineffective on a resistant line of Yoshida tumour and on a number of other transplantable tumours. The action of DBD on the alterations in nucleic acid contents of sensitive and resistant tumours was investigated. The changes especially in the RNA content were much more characteristic in sensitive tumours than in resistant ones. Contrary to tumour tissue, a more marked decrease in the DNA content of bone marrow was observed, while the changes in the RNA content were not so extensive. In addition, the time necessary for regeneration was shorter in the bone marrow than in the tumour tissue. 100 μg/ml DBD inhibited the 14C-thymidine, and increased the 14C-orotic acid incorporation into the nucleic acids of sensitive Yoshida tumour cells in vitro. However, no alteration occurred in the rate of incorporation of the labelled precursors in resistant or refracter tumour cells in the presence of DBD in vitro. The increased RNA synthesis occurring in sensitive tumour cells could not be depressed by actinomycin D. These changes in the synthetic activities taking place in the sensitive tumour cannot be considered as the site of action of DBD because lower concentration of the drug (25-50 μg/ml) proved to be sufficient to decrease the viability of sensitive tumour cells in vitro. Therapeutic dose of DBD increased the synthesis of a RNA fraction in the sensitive tumour cells also in vivo. The nature of this RNA species is so far unknown. DBD does not alter the thermal denaturation profile of DNA so it seems unlikely that the drug interferes with the template function of DNA, like other alkylating agents. © 1969.