Studies of the effects of associated photodynamic therapy and drugs on macromolecular synthesis of tumoral cells grown in vitro.

V F Dima, I N Mihăilescu, S V Dima, L Chivu, M Stirbeţ, M Udrea, A Popa
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Abstract

HeLa S3 tumoral cells were used as an experimental model for studying the association of photodynamic therapy (PDT) and antitumoral agents. Tumoral monolayer cultures were incubated 18 hours at 37 degrees C with Photofrin II, trypsinized and suspended in Eagle medium supplemented with 10% FCS and then treated with antitumoral agents 90 minutes before He-Ne laser exposure. The tumoral cells were exposed to antitumoral agents in the following concentrations (equivalent to ED70): adriamycin (0.0297 micrograms); mitomycin C (0.0199 micrograms); 5-FU (0.4937 micrograms) and vinblastine (0.0109 micrograms) per 10(5) cells. Macromolecular syntheses (DNA, RNA and proteins) were investigated by use of radioactive precursors: 3H-thymidine, 3H-uridine and 3H-leucine, as expressed in percent referring to Photofrin II-pretreated controls; they were exposed to He-Ne laser but not treated with antitumoral agents. All experiments were followed for 72 hours incubation at 37 degrees C. The conclusions of the results of PDT associated with antitumoral agents sustain the following aspects: a) the antitumoral agents activity (adriamycin, mitomycin C, 5-FU, vinblastine) was more noticeable when applied 90 minutes before He-Ne laser irradiation; b) inhibition of radioactive precursors uptake in DNA, RNA and proteins was accompanied by suppression of in vitro tumoral cells development and c) PDT association with antitumoral agents could manifest at least three positive effects upon animals; 1) PDT potentiating effects with antitumoral agents; 2) suppressing effects on tumoral macromolecular synthesis; 3) antitumoral agents cytotoxic elimination (due to the low doses used).

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相关光动力疗法及药物对体外培养肿瘤细胞大分子合成影响的研究。
以HeLa S3肿瘤细胞为实验模型,研究光动力治疗(PDT)与抗肿瘤药物的相关性。肿瘤单层培养物在37℃下与Photofrin II孵育18小时,胰蛋白酶化并悬浮在添加10% FCS的Eagle培养基中,然后在He-Ne激光照射前90分钟用抗肿瘤药物处理。肿瘤细胞暴露于以下浓度的抗肿瘤药物(相当于ED70):阿霉素(0.0297微克);丝裂霉素C(0.0199微克);5- fu(0.4937微克)和长春花碱(0.0109微克)每10(5)个细胞。使用放射性前体:3h -胸腺嘧啶、3h -尿嘧啶和3h -亮氨酸(参照Photofrin ii预处理对照,以百分比表示)研究大分子合成(DNA、RNA和蛋白质);他们暴露在He-Ne激光下,但没有使用抗肿瘤药物治疗。37℃孵育72 h, PDT与抗肿瘤药物相关的实验结果表明:a)在He-Ne激光照射前90 min,抗肿瘤药物(阿霉素、丝裂霉素C、5-FU、长春花碱)的活性更为显著;b)抑制放射性前体对DNA、RNA和蛋白质的摄取,同时抑制体外肿瘤细胞的发育;c) PDT与抗肿瘤药物的关联在动物身上至少表现出三种积极作用;1)抗肿瘤药物对PDT的增强作用;2)抑制肿瘤大分子合成;3)抗肿瘤药物细胞毒性消除(由于使用剂量低)。
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