Koul Ashwani, Kaur Navneet, Chugh Neha Arora
a Department of Biophysics , Panjab University , Chandigarh , India.
J Diet Suppl. 2018 Jan 2;15(1):72-87. doi: 10.1080/19390211.2017.1322659. Epub 2017 May 17.
The present study was aimed at investigating the modulatory effects of folic acid (FA) on early stages of chemically induced skin cancer. For this, a two-stage model of skin tumorigenesis was employed. 7,12-Dimethylbenz(a)anthracene (DMBA, 500 nmol/100 ul of acetone) was applied topically for two weeks (twice weekly), followed by phorbol-12-myristate-13-acetate (TPA, 1.7 nmol/100 ul) twice weekly for six weeks on the depilated skin of mice, and FA was administered orally at a dose of 40 microgram/animal for 10 weeks daily. Balb/c mice were divided into four groups depending upon the treatment they received (control, DMBA/TPA, FA, and FA+DMBA/TPA). DMBA/TPA treatment led to the formation of papillomas in DMBA/TPA and FA+DMBA/TPA groups. Ornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA), epidermal thickness, and cell count were evaluated to assess the beneficial effects in the early stages. FA exhibited its ameliorative potential as indicated by decreased epidermal thickness and cell count in FA+DMBA/TPA group when compared to DMBA/TPA group. Concomitantly, FA decreased the expression of ODC and PCNA in skin and activity of serum lactate dehydrogenase, suggesting inhibitory effects on cell proliferation and cell damage. Differential modulation in lipid peroxidation and reduced glutathione was observed in response to DMBA/TPA treatment and its intervention with FA. Although these findings suggest the inhibitory potential of FA during initial stages of murine skin cancer, detailed studies are warranted considering the ambiguous reports available in literature regarding the association of FA and cancer.
本研究旨在探讨叶酸（FA）对化学诱导的皮肤癌早期阶段的调节作用。为此，采用了皮肤肿瘤发生的两阶段模型。将7,12-二甲基苯并(a)蒽（DMBA，500 nmol/100 μl丙酮）局部涂抹于小鼠脱毛皮肤上，每周两次，持续两周，随后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），持续六周，同时每天以40微克/动物的剂量口服FA，持续10周。根据所接受的治疗，将Balb/c小鼠分为四组（对照组、DMBA/TPA组、FA组和FA+DMBA/TPA组）。DMBA/TPA处理导致DMBA/TPA组和FA+DMBA/TPA组形成乳头状瘤。通过评估鸟氨酸脱羧酶（ODC）、增殖细胞核抗原（PCNA）、表皮厚度和细胞计数来评估早期阶段的有益效果。与DMBA/TPA组相比，FA+DMBA/TPA组的表皮厚度和细胞计数降低，表明FA具有改善潜力。同时，FA降低了皮肤中ODC和PCNA的表达以及血清乳酸脱氢酶的活性，表明对细胞增殖和细胞损伤具有抑制作用。在对DMBA/TPA处理及其与FA的干预反应中，观察到脂质过氧化和还原型谷胱甘肽存在差异调节。尽管这些发现表明FA在小鼠皮肤癌初始阶段具有抑制潜力，但考虑到文献中关于FA与癌症关联的报道不明确，仍需进行详细研究。
