Balsari A, Lombardo N, Ghione M
Inst. of Medical Microbiology, University of Milan, Italy.
J Chemother. 1989 Oct;1(5):324-9. doi: 10.1080/1120009x.1989.11738916.
Extravasation of antitumor drugs and particularly doxorubicin (DXR) can be followed by skin ulceration and slowly evolving perivascular necrosis. DXR lesions have some characteristics in common with those induced by ionizing radiation and, with respect to gross morphology, are reminiscent of skin lesions induced by necrotizing agents. Time course and histopathology of toxic phenomena induced by intradermal or perivascular injection of various doses of either DXR or caustic chemicals have been studied in hairy outbred and hairless inbred (MF1 hr/hr) mice. The latter strain has been found to be intrinsically more sensitive to DXR induced toxic effects, particularly as far as perivascular administration is concerned. Long lasting lesions and, in a few cases, systemic involvement have been observed. On the contrary, necrotic foci induced by caustic chemicals rapidly regressed in both strains. The perivascular administration model, which has not been previously investigated, appears to be representative of what happens in clinical conditions and can be of use for assessing either skin toxicity of antitumor compound or the protective effect of candidate antidotes.
抗肿瘤药物，尤其是阿霉素（DXR）外渗后，可能会出现皮肤溃疡和逐渐发展的血管周围坏死。DXR损伤与电离辐射诱导的损伤有一些共同特征，从大体形态学来看，类似于坏死剂诱导的皮肤损伤。在有毛远交系和无毛近交系（MF1 hr/hr）小鼠中，研究了皮内或血管周围注射不同剂量的DXR或腐蚀性化学物质所诱导的毒性现象的时间进程和组织病理学。已发现后一种品系对DXR诱导的毒性作用本质上更敏感，尤其是在血管周围给药方面。观察到了持久的损伤，在少数情况下还出现了全身受累。相反，腐蚀性化学物质诱导的坏死灶在两个品系中均迅速消退。血管周围给药模型此前未被研究过，似乎代表了临床情况下发生的情况，可用于评估抗肿瘤化合物的皮肤毒性或候选解毒剂的保护作用。
