抗癌剤投与が誘発舌癌の腫瘍血管内皮細胞におよぼす影響に関する電顕的研究

特にTHP-ADM, CDDP, PEP 併用による物質透過関連構造の動態について

抄録

The purpose of this study is to determine the ultrastructural changes of tumor blood vessels (TBV) and the permeability of endothelium after multiple agent combination therapy in Golden hamsters with squamous cell carcinoma of the tongue induced by dimethyl 1, 2-benzanthracene acetone solution (DMBA). The animals were divided into normal tongue (control) and DMBA-induced carcinoma (experimental) groups. They were then given intraperitoneal injection of isotonic saline, Pirarubicin (THP-ADM) alone, combination of Cisplatin (CDDP) and Peplomycin (PEP) (PP combination), or a combination of THP-ADM, CDDP and PEP (TPP combination). Tannic acid solution was injected as a tracer via the heart, and the vasculature was perfused with half-strength of Karnovsky’s fixative 15 seconds later. The ultrastructual changes of capillaries surrounding the cancer nests were observed by transmission electron microscopy. Compared to the control group, TBV in the experimental group demonstrated many morphological changes such as thinning of the endothelial cells, increase of fenestrae in each endothelial cell, decrease in pinocytotic vesicles, appearance of Weibel-Palade body and discontinuity of basal lamina. Administration of the THP-ADM alone resulted in a remarkably greater increase in pinocytotic vesicles than did saline, PP and TPP combinations in both control and experimental groups. TPP combination in the experimental group induced remarkable thinning of endothelial cells, a significantly decrease in pinocytotic vesicles, significant increase in fenestrae and frequent formation of transendothelial channel, compared to treatment with saline, THP-ADM alone and PP combination. Permeation through TBV varied with a reaction of endothelial cells to the antitumor agents, morphological feature of basal lamina and changes in surrounding connective tissue. The pattern of endothelial permeability after administration of THP-ADM differed among animals treated with THP-ADM alone and those with TPP combination. The results suggested that macromolecular permeability of vascular endothelial cells was augmented by preadministration of THP-ADM.