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  • Title: Relative pulmonary toxicity and antitumor effects of two new bleomycin analogs, pepleomycin and tallysomycin A.
    Author: Sikic BI, Siddik ZH, Gram TE.
    Journal: Cancer Treat Rep; 1980; 64(4-5):659-67. PubMed ID: 6159079.
    Abstract:
    The relative therapeutic and toxic effects of two new analogs were compared with bleomycin over a range of doses. Therapeutic effects were determined in mice bearing Lewis lung carcinoma and B16 melanoma. On a milligram-per-kilogram basis, tallysomycin A was two to three times as potent as bleomycin in inhibiting the growth of these two experimental solid tumors in vivo. However, tallysomycin A was also two to three times as potent as bleomycin in producing pulmonary toxic effects. Lethality and skin toxicity were similarly increased. Pepleomycin, on the other hand, 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 also had a peculiar central nervous system toxicity characterized by hyperirritability and persistent gyrating movements of the animals. Thus, there are distinct quantitative as well as qualitative differences in the therapeutic and toxic properties of these two analogs compared to bleomycin.
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