Arora N, Bansal M P, Koul A
Department of Biophysics, Panjab University, Chandigarh 160014, India.
Indian J Biochem Biophys. 2013 Apr;50(2):105-13.
The modulation in biochemical status of skin and hepatic tissue at the time point of commencement of promotion stage of skin carcinogenesis in mice and its intervention with aqueous Azadirachta indica leaf extract (AAILE) were investigated. 7,12-Dimethylbenz(a)anthracene (DMBA, 500 nmol/100 ul of acetone) was applied topically for 2 weeks (twice weekly), followed by phorbol-12-myristate-13-acetate (TPA, 1.7 nmol/100 ul) twice weekly for 6 weeks on the depilated skin of mice and AAILE was administered orally at a dose level of 300 mg/kg body wt thrice a week for 10 weeks. DMBA/TPA treatment upregulated the phase I enzymes in skin and hepatic tissue, as revealed by the increased cytochrome P450 (CYP) and cytochrome b5 (cyt b5) levels and aryl hydrocarbon hydroxylase (AHH) activity when compared to the control group and differentially modulated the activities of phase II enzymes like glutathione-s-transferase (GST), DT-diaphorase (DTD) and uridine diphosphate glucuronosyltransferase (UDP-GT). AAILE treatment decreased the DMBA/TPA-induced increase in cutaneous CYP level and enhanced the DTD and UDP-GT activities when compared with DMBA/TPA group. In the hepatic tissue of AAILE + DMBA/TPA group, an increase in UDP-GT activity was observed when compared to DMBA/TPA group. DMBA/TPA treatment did not alter the skin lipid peroxidation (LPO) level when compared to control group, however, in the animals that received AAILE treatment along with DMBA/TPA, a significant increase in LPO was observed when compared to control group. This was associated with a decrease, in cutaneous reduced glutathione (GSH) level of AAILE + DMBA/TPA group. Enhanced LPO level was observed in the hepatic tissue of DMBA/TPA and AAILE + DMBA/TPA groups when compared to control group. However, no alteration was observed in their hepatic GSH levels. The micronuclei score in hepatic tissue did not exhibit significant inter-group differences. The results of the present study suggest that apart from skin, liver may be affected during DMBA/TPA-induced skin tumorigenesis. AAILE treatment has the ability to modulate these changes potentially influencing the process of tumor formation. These findings seem to be important to carcinogenesis and its intervention with anti-cancer agents.
研究了小鼠皮肤癌发生促进阶段开始时皮肤和肝组织生化状态的变化及其与印度楝树叶水提取物（AAILE）的干预作用。将7,12-二甲基苯并(a)蒽（DMBA，500 nmol/100 μl丙酮）局部涂抹2周（每周两次），随后在小鼠脱毛皮肤上每周两次涂抹佛波醇-12-肉豆蔻酸酯-13-乙酸酯（TPA，1.7 nmol/100 μl），共6周，AAILE以300 mg/kg体重的剂量每周口服三次，共10周。与对照组相比，DMBA/TPA处理上调了皮肤和肝组织中的I相酶，表现为细胞色素P450（CYP）、细胞色素b5（cyt b5）水平升高以及芳烃羟化酶（AHH）活性增加，并且对II相酶如谷胱甘肽-S-转移酶（GST）、DT-黄递酶（DTD）和尿苷二磷酸葡萄糖醛酸转移酶（UDP-GT）的活性进行了差异调节。与DMBA/TPA组相比，AAILE处理降低了DMBA/TPA诱导的皮肤CYP水平升高，并增强了DTD和UDP-GT的活性。在AAILE + DMBA/TPA组的肝组织中，与DMBA/TPA组相比，观察到UDP-GT活性增加。与对照组相比，DMBA/TPA处理未改变皮肤脂质过氧化（LPO）水平，然而，在接受AAILE与DMBA/TPA联合处理的动物中，与对照组相比，观察到LPO显著增加。这与AAILE + DMBA/TPA组皮肤中还原型谷胱甘肽（GSH）水平降低有关。与对照组相比，在DMBA/TPA组和AAILE + DMBA/TPA组的肝组织中观察到LPO水平升高。然而，它们的肝GSH水平未观察到改变。肝组织中的微核评分在组间未表现出显著差异。本研究结果表明，除皮肤外，肝脏在DMBA/TPA诱导的皮肤肿瘤发生过程中可能也会受到影响。AAILE处理具有调节这些变化的能力，可能会影响肿瘤形成过程。这些发现似乎对肿瘤发生及其抗癌药物干预具有重要意义。
