不同组分的57Co(钴57)——争光霉素在肿瘤动物中的分布特性及其与抑瘤和毒性关系的探讨

⁵⁷Co标记的七种争光霉素组分(A₂+B₂混合品、A₂、A₄、A₅、A₆、A₅₀₃₃和B₂)在实体型艾氏腹水癌小鼠的分布实验中,发现七种组分都亲瘤和抑瘤。争光霉素A₅和A₆的亲瘤性最高。用等毒性剂量,A₅、A₄和A₂具有最高的抑瘤性。小鼠肝、肾和肿瘤对各种标记的争光霉素组分的摄取以A₅₀₃₃为最低,A₆为最高,因此目前看来,以A₆进行临床试用的前景似比其他的组分为差。A₅₀₃₃在肺中集聚少,排出较快,急性毒性又最低,按相等的LD₅₀剂量给药其抑瘤率也较高,从减少肺纤维化这点考虑,它可能是值得进一步研究的。A₅亲瘤抑瘤较高,肾和肝摄取较高,但较A₆为低,排出较慢,在体内保留时间较长,也是一种有发展前途的单一争光霉素组分。

DISTRIBUTION OF VARIOUS 57Co-LABELLED ZHENGGUANGMYCIN PREPARATIONS IN EHRLICH CARCINOMA BEARING MICE IN RELATION WITH THEIR ANTITUMOR ACTIVITY AND TOXICITY

The distribution of various ⁵⁷Go-labelled Zhengguangmycin preparations, namely: single natural components A₂, A₄, A₅, A₆, B₂, a mixed preparation comprising of components A₂+B₂, and a single component derivation A₅₀₃₃ was studied in mice bearing solid type Ehrlich carcinoma. It was found that all these preparations exhibited antitumor and tumortropic properties. Among all the preparations, components A₅ and A₆ exhibited the strongest tumor-tropic property.Given at equivalent toxicity dosage (1/20 LD₅₀, components A₅ and A₄ exhibited the highest rate of tumor inhibition. The uptake of radioactivity in the mouse liver, kidney and tumor was the highest with component A₆ and the lowest with preparation A₅₀₃₃. It appears that A₆ would be the least promising component for clinical trial. The preparation A₅₀₃₃, beside the above mentioned properties, has the additional advantage of having a low uptake in the lung, rapid excretion through the kidney and the lowest acute toxicity. Moreover, A₅₀₃₃ exhibited a satisfactory tumor inhibition rate as compared with other prepations when given at equivalent toxicity dosage. It therefore appears to be worthy of further investigation from the point of diminishing pulmonary fibrosis. Though the uptake of component As in the mouse kidney and liver was rather high, yet it was lower than that of A₆. It was excreted slowly through the urine. On the ground that As has the strongest tumor inhibitory activity and a better retention in the animal body, it would also appear to be a component worthy of further study as an antitumor agent.