Verma A K
Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
Prev Med. 1989 Sep;18(5):646-52. doi: 10.1016/0091-7435(89)90035-2.
DL-alpha-Difluoromethylornithine (DFMO) is an enzyme-activated irreversible inhibitor of mammalian ornithine decarboxylase. DFMO, when administered in drinking water, precludes increases in the levels of intracellular putrescine and spermidine and also inhibits the induction of skin, breast, colon, urinary bladder, and intestinal cancers in experimental animal models. DFMO may be a useful drug for cancer prevention in humans; however, long-term medication with higher doses (9 g/m2/day) of DFMO has resulted in several toxic side effects such as thrombocytopenia and reversible ototoxicity. Smaller doses (less than 1 g/m2/day), selected by our in vitro human skin punch biopsy assay, may be given for a longer period without appreciable toxicity. Further evaluation in human cancer prevention trials is indicated.
DL-α-二氟甲基鸟氨酸（DFMO）是一种酶激活的哺乳动物鸟氨酸脱羧酶不可逆抑制剂。当通过饮用水给药时，DFMO可防止细胞内腐胺和亚精胺水平升高，并抑制实验动物模型中皮肤癌、乳腺癌、结肠癌、膀胱癌和肠道癌的诱发。DFMO可能是一种对人类癌症预防有用的药物；然而，长期服用高剂量（9 g/m²/天）的DFMO会导致多种毒副作用，如血小板减少和可逆性耳毒性。通过我们的体外人体皮肤打孔活检试验选择的较小剂量（小于1 g/m²/天），可以在没有明显毒性的情况下给予更长时间。有必要在人类癌症预防试验中进行进一步评估。
