The distribution of [3H]vinblastine in tumor and host tissues of Nb rats bearting a transplantable lymphoma which is highly sensitive to the alkaloid.

A new transplantable lymphoma in Nb rats responded dramatically to treatment with vinblastine (VLB). A single i.p. injection of VLB, 0.8 mg/kg, caused even highly advanced tumors to regress until they were no longer palpable. or investigation of the hypothesis that the oncolytic response may reflect a special affinity of VLB for the tumor, lymphoma-bearing rats were given an i.p. injection of -e13H]VLB, and the levels of radioactivity and [3H]VLB in the tumor and host tissues were determined as a function of time. Radioactivity was concentrated by the lymphoma relative to the blood (mostly as unchanged [3H]VLB) at levels that showed only a modest decline over a period of at least 48 hr. During this time the [2H]VLB in both the plasma and whit blood cell fraction of the blood declined markedly and continuously to very low levels. Thymus and lymph nodes resembled the lymphoma in showing a long-term retention of radioactivity. The levels of radioactivity in the spleen, liver, and bone marrow were initially much higher than that in the tumor but decreased markedly with time. In addition very little of the radioactivity remaining in the spleen and liver at 48 hr was due to [3H]VLB, and by this time the VLB concentration in these tissues was much lower than in the tumor. It is suggested that the chemotherapeutic response of the lymphoma may be related to the continuing presence of a significant concentration of VLB in this tumor after the plasma VLB had fallen to very low (subantimitotic) levels.

Induction of alkaline phosphatase in cultured human fibroblasts. Comparison of normal cells and those from patients with cystic fibrosis.

The membrane glycoprotein enzyme, alkaline phosphatase was induced in cultured human fibroblasts by dibutyryl cyclic AMP, sodium butyrate, the serum glycoprotein fetuin, the Tamm-Horsfall urinary glycoprotein, and by a number of inhibitors of DNA synthesis. The uninduced basal enzyme activity increased at later stages of growth when the cells became confluent. Induction by dibutyryl cyclic AMP or fetuin was most effective when the agents were added after the cells had reached stationary phase and was maximal after at least two days of exposure. The levels of induction resulting from the addition of pairs of the agents, dibutyryl cyclic AMP, n-butyrate and fetuin were additive indicating that these have different modes of action. The inhibitors of DNA synthesis, cytosine arabinoside, hydroxyurea, and methothrexate were less effective inducers. Bromodeoxyuridine which also has non-DNA mediated effects induced to the same extent as dibutyryl cyclic AMP. Similar experiments with sex- and age-matched cell strains derived from patients with cystic fibrosis failed to detect differences in the levels of induction from those observed in normal cells. In addition, the combined inductive effects of Tamm-Horsfall glycoprotein, isoproterenol and theophylline, were similar with normal and cystic fibrosis cells.