목적 : Paclitaxel(Taxol)은 미소관의 집합을 촉진시키고 분해를 방지하여 세포주기 중 유사분열을 정지시킴으로써 방사선조사와 병용할 경우 방사선감작제로서의 가능성이 있다. 정상세포 중 횐쥐의 소장에서 paclitaxel이 방사선의 독성을 증가시키는지 알기 위하여 실험을 시도하였다. 대상 및 방법 : Paclitaxel군은 paclitaxel 10mg/kg을 복강내 1회 주입하였다. 방사선조사군은 8 Gy를 전복부에 단일조사하였다. Paclitaxel과 방사선병용군은 paclitaxel(10mg/kg)을 복강내 주입 후 24시간에 방사선조사군과 동일한 방법으로 조사하였다. 실험완료 후 소장점막에서 유사분열수, apoptosis와 기타 점막의 변화를 시간별로(6시간 -5일) 관찰하였다. 결과 : Paclitaxel은 소장점막의 소낭선세포에서 유사분열을 정지시키며 약간의 apoptosis을 유발하였으며 유사분열정지는 6시간에서 최대치를 보였고 24시간에 정상으로 회복되었다. 방사선조사는 apoptosis를 유발하였으며 6시간에 최대치를 보이고 24시간에 정상으로 회복되었다. Paclitaxel과 방사선병용군에서 유사분열정지는 6시간에서 3일까지 나타났으며 apoptosis는 6시간과 24시간에 약간 보였으며 3일에 정상으로 회복되었다. 병용군에서 apoptosis의 빈도는 정상군보다 높았으나 방사선단독군에 비하여 현저하게 감소되어 방사선보호작용이 있었다. 결론 : Paclitaxel에 의한 유사분열정지는 6시간에 최대치를 보이고 24시간에 정상으로 회복 되었으며 약간의 apoptosis을 유발하였다. 방사선조사는 apoptosis를 유발하였으며 6시간에 최대치를 보이고 24시간에 정상으로 회복되었다. 정상 소장에 방사선조사를 paclitaxel주입 후 24 시간에 시행하여 apoptosis가 방사선조사군에 비하여 현저히 감소되어 paclitaxel이 방사선보호작용이 있었다.
Purpose : Paclitaxel is a chemotherapeutic agent with potent microtubule stabilizing activity that arrests cell cycle in $G_2$-M Because $G_2$-M is the most radiosensitive Phase of the cell cycle, paclitaxel has potential as a cell cycle- specific radiosensitizer. This study was designed to investigate the ability of paclitaxel to increase the radiotoxicity in normal small bowel mucosa of the rat. materials and Methods : A sigle intraperitoneal infusion of paclitaxel (10mg/kg), and a single irradiation(8 Gy, x-ray) to the whole abdomen and combination of radiation(8 Gr, x-ray) 24 hours after paclitaxel infusion in the rats were done. The changes of jejunal mucosa, and kinetics of mitotic arrest and apoptosis in the jejunal crypt were defined at 6 hours - 5 days after each treatment histologically. Results : Paclitaxel blocked jejunal crypt cell in mitosis and induced minmal apoptosis. Mitotic arrest by paclitaxel was peaked at 6 hours after infusion and returned to normal by 24 hours. Radiation induced apoptosis and peaked at 6 hours and returned to normal by 24 hours. Combination of paclitaxel and radiation blocked crypt cell in mitosis at 3 days and induced apoptosis slightly at 6 hours and 24 hours and returned to normal by 3 days. The incidence of apoptosis in combined group at 6 hours was slightly higher than normal control but significantly lower than radiation alone group. The major changes of jejunal mucosa were nuclear vesicle and atypia which were appeared at 6 hours - 3 days and returned to normal by 5 days The degree of the mucosal changes are not different in 3 groups except for absence of inflmmatory reaction in radiation group. Conclusion : Mitotic arrest by paclitaxel was peaked at 6 hours and returned to normal by 24 hours and paclitaxel induced minimal apoptosis. Radiation induced apoptosis, peaked at 6 hours and returned to normal by 24 hours. Radiation-induced apoptosis was less in combined group which suggested that paclitaxel have a radioprotective effect when radiation was given 24 hours after paclitaxel infusion.
