Villiotou V, Deliconstantinos G
Department of Experimental Physiology, University of Athens Medical School, Greece.
Anticancer Res. 1995 May-Jun;15(3):931-42.
Ultraviolet A (UVA) irradiated human squamous cell carcinoma (SCC-13) releases nitrogen oxides, i.e. nitric oxide (NO), peroxynitrite (ONOO-), nitrosocompounds, ammonia (NH3) and hydroxylamine (H2NOH) formed from L-arginine. Formation and/or release of these nitrogen oxides was time and concentration-dependently stimulated by UVA and decreased by N-monomethyl-L-arginine (L-NMMA), a compound that inhibits NO synthase activity. UVA irradiation of SCC-13 cells resulted in concomitant increase in soluble guanylate cyclase (sGC) which was inhibited by L-NMMA. The increased NO and ONOO- production evoked by dibutyryl cGMP and 3-isobutyl-l-methyl-xanthine (IBMX) represents an additional positive feedback mechanism that could serve to maintain NO and ONOO- release for extended periods following UVA radiation. Using an in vitro chemical model system, it was demonstrated that oxidation of NH3 to NO by hydroxyl radical (.OH) at physiological pH is chemically feasible. UVA irradiated SCC-13 cells induced a luminol-enhanced chemiluminescence signal that reaches a peak within 1 min. The modulation of this signal by ebselen is consistent with a rate-determining step corresponding to the disproportionation of a luminol-superoxide (O2-) complex. UVA irradiated SCC-13 cells promptly increased malondialdehyde (MDA) production with subsequent decrease of plasma membrane fluidity. Desferrioxamine tested in UVA irradiated SCC-13 cells showed a concentration dependent decrease in MDA production with subsequent restoration of the membrane fluidity to the normal level. Furthermore, it was shown that squamous cell carcinoma possesses higher NO synthase and sGC activity as compared to normal keratinocytes. Such an increase in NO production may be directly related to the poor prognosis of squamous cell carcinoma.
紫外线A（UVA）照射人鳞状细胞癌（SCC - 13）会释放氮氧化物，即一氧化氮（NO）、过氧亚硝酸盐（ONOO-）、亚硝基化合物、氨（NH3）以及由L - 精氨酸形成的羟胺（H2NOH）。这些氮氧化物的形成和/或释放受到UVA的时间和浓度依赖性刺激，并被抑制一氧化氮合酶活性的化合物N - 甲基 - L - 精氨酸（L - NMMA）所降低。UVA照射SCC - 13细胞导致可溶性鸟苷酸环化酶（sGC）同时增加，而L - NMMA可抑制这种增加。二丁酰环磷鸟苷（dibutyryl cGMP）和3 - 异丁基 - 1 - 甲基黄嘌呤（IBMX）引起的NO和ONOO-生成增加代表了一种额外的正反馈机制，该机制可在UVA辐射后长时间维持NO和ONOO-的释放。使用体外化学模型系统证明，在生理pH值下，羟自由基（·OH）将NH3氧化为NO在化学上是可行的。UVA照射的SCC - 13细胞诱导鲁米诺增强的化学发光信号，该信号在1分钟内达到峰值。依布硒啉对该信号的调节与鲁米诺 - 超氧化物（O2-）复合物歧化反应的速率决定步骤一致。UVA照射的SCC - 13细胞迅速增加丙二醛（MDA）的产生，随后细胞膜流动性降低。在UVA照射的SCC - 13细胞中测试的去铁胺显示MDA产生呈浓度依赖性降低，随后膜流动性恢复到正常水平。此外，研究表明，与正常角质形成细胞相比，鳞状细胞癌具有更高的一氧化氮合酶和sGC活性。这种NO产生的增加可能与鳞状细胞癌的不良预后直接相关。
