RELATIVE PULMONARY TOXICITY AND ANTI-TUMOR EFFECTS OF 2 NEW BLEOMYCIN ANALOGS, PEPLEOMYCIN AND TALLYSOMYCIN-A

  • 1 January 1980
    • journal article
    • research article
    • Vol. 64  (4-5) , 659-667
Abstract
The relative therapeutic and toxic effects of 2 new analogs were compared with bleomycin over a range of doses. Therapeutic effects were determined in mice bearing [mouse] Lewis lung carcinoma cells and [mouse] B16 melanoma cells. On a milligram-per-kilogram basis, tallysomycin A was 2 to 3 times as potent as bleomycin in inhibiting the growth of these 2 experimental solid tumors in vivo. Tallysomycin A was also 2 to 3 times as potent as bleomycin in producing pulmonary toxic effects. Lethality and skin toxicity were similarly increased. Pepleomycin was approximately equivalent to bleomycin in antitumor potency but exhibited significantly less pulmonary toxicity. Despite this decreased lung toxicity, pepleomycin was more lethal, with 50% and 100% mortality at doses which produced 0 and 19% mortality, respectively, in mice treated with bleomycin. Pepleomycin had a peculiar CNS toxicity characterized by hyperirritability and persistent gyrating movements of the animals. There are distinct quantitative and qualitative differences in the therapeutic and toxic properties of these 2 analogs compared to bleomycin.