Modification of the State of Adrenergic Systems: Effects on Experimental Tumor Growth and Antitumor Activity of Chlofiden

We studied the effects of treatments with adrenaline hydrochloride, obsidan (a -adrenoblocker), melipramine (an inhibitor of monoamine uptake by neurons), and reserpine (a sympatholytic drug) on tumor growth (Pliss' lymphosarcoma in rats) and on the antitumor activity of a novel cytostatic drug, chlofiden. We found that adrenaline and reserpine enhanced the antitumor effect of chlofiden. Isolated applications of adrenaline and melipramine exerted slight antitumor effects, while after reserpine treatment there was a trend toward stimulation of tumor growth. Under the conditions of the model used, obsidan demonstrated no noticeable antitumor activity and did not modify the antitumor effect of chlofiden. Possible mechanisms of the observed effects are discussed.     

Cytotoxic effect of antineoplastic substances and their effect on DNA synthesis and cGMP level in tumor and normal tissues

The cytostatic effect of antitumour agents line on the level of malignantly changed actively proliferating system (tumour growth) and normal actively proliferating system (splin) was investigated on the basis of DNA synthesis and cGMP rate. Studies of these antitumour agents were carried out on three tumour growth models (Pliss lymphosarcoma, Yablonovskaya glyoblastoma and human glyoblastoma heterografts (subcapsular test). It has been demonstrated that chlofiden, brotheophine, vincristine, adriablastine, natulan, phthorafur have a marked and stable effect of DNA synthesis inhibition, resulting in their marked cytostatic effect and antitumour action stability under the therapy conditions. The experimental data have shown cGMP rates decrease in Pliss lymphosarcoma in the case of high antitumour activity.     

Effects of modulation of the cholinergic system activity on the experimental tumor growth and antitumor activity of chlofiden

We studied the influence of an anticholinesterase agent, proserine, and an m-cholinoblocker, atropine, on the growth of Pliss lymphosarcoma in rats and on the antitumor activity of a cytotoxic drug, chlofiden. It has been demonstrated that proserine stimulates tumor growth and decreases the antitumor efficacy of chlofiden. Injections of atropine evoked opposite effects: inhibition of the tumor growth and an increase in the, antitumor activity of chlofiden. Possible mechanisms of the above effects are discussed.