Jasmine Naranjo
Professor Steel, Christina
BIOL 293
Fall 2018
Reduction in squamous cell carcinomas in mouse skin by dietary zinc supplementation
“Thoughts flit in and out of my mind like floating white dandelion seed-heads. What if the mole is cancerous?” by Helen Libby, Skin Deep
It is estimated that approximately 9,500 people in the U.S. are diagnosed with skin cancer every day. Research estimates that nonmelanoma skin cancer, including basal cell carcinoma and squamous cell carcinoma, affects more than 3 million Americans a year. My interest in this article was due to my passion in public health, I aspire to be involved in research especially in different types of cancers. Public health is a career field I have chosen for myself to help insure improvements in medical advances, drug developments, and the safety of the population. The article was a study of Zinc supplementation, replenishment in Zinc-deficient, and Zinc sufficient mice to reverse tumor burdens and histopathological grade. The mice were on a regimen of Zinc supplementation in the drinking water and found that the Zinc sufficient cohort benefited from supplemental Zn during forestomach carcinogenesis, resulting in decrease in tumor number and severity of preneoplastic and neoplastic lesions.
The study began using C57BL/6J noted on chats as (B6) wild type (wt) mice that are natural resistant to skin cancers and Fhit mice which are the “knockout mice” (Fhit, murine fragile histidine triad gene) both in Male and Female each. The experiment was for twenty weeks and it was performed on the small cohorts using the same mouse strains, treatment protocol was with and without the Zinc supplementation to gage timing of tumor beginning in the different mouse strains and genders. Figure 1A is a graph of tumor Initiation/latency in the first 20 weeks without Zinc supplementation of both male and female mice with both strains. In addition, the control mice received standard water ad libitum verses the treatment group. Figure 1A-H showed slides of the mice papilloma from Fhit female without Zn. B, mild hyperplasia from a wt male with Zn treatment. C, sever hyperplasia from Fhit female with Zn treatment. D, dysplasia from Fhit female with Zn treatment. E, a poor differentiated SCC with cohorts of an atypical tumor cells diffusely infiltrating into the stroma and skeletal muscle from fhit female without Zinc. F, well-differentiated SCC, with mild cytologic atypia from a wt female without Zinc. G, moderately differentiated SCC with enlarged tumor cells and prominent nucleoli. H, a well- differentiated SCC in subcutaneous are invasive from a wt male with Zn treatment. Once the experiment was terminated, skin, liver, spleen, and kidney were grossly examined for tumors, and skin sections were cut across all layers and stood on cut-end slides.
Squamous cell carcinomas were categorized based on three differentiation levels; poorly, moderately, well differentiated. The results summarized that the un-supplemented fhit mice exhibited significantly more skin tumors following DMB/PMA treatment than wt mice with an average of 16.6 versus 7.6 total tumors per mouse, (P< 0.001). Both Female and male Fhit−/− mice had similar total tumors (16.5/mouse for females and 15.9/mouse for males) whereas there was a slight bias for tumors in female wt mice (9.1/mouse for females vs. 6.0/mouse in males, P = 0.07). It showed that the Zinc supplement significantly reduced total average and gender-specific tumor burdens in hit mice, while fhit mice given non-supplementation drinking water developed more tumors (average, 16.2/ mouse) compared to those on Zn-gluconate water (10.3/ mouse), a 37% decrease with Zn supplementation (P < 0.001). However, the tumor burden reductions were different for both female and male mice; the female mice showed 49% reduced tumor burden after Zn treatment versus the 25% for male mice. There was a decrease in the total number of large tumors for both male and female wt mice with Zn supplement due to the combined resistance. One of the burdens is inflammation; since inflammation is a contributing factor to carcinogenesis, it did show significant reduction in inflammation with Zinc supplementation of B6 male skin tumors. However, fhit mice did show changes in inflammation after supplementation but not as significant as the B6 mice due to involved mechanisms other than or in addition to effects on inflammatory process.
Therefore, there was significant improvements on the burden of squamous cell carcinomas in mouse skin by dietary Zinc supplement. The study related to cells due to a squamous cell carcinoma is a cell; they are small flat cells in the outer layer of skin. Which slowly grows then it usually occurs on areas of the skin were its repeatedly exposed to strong sunlight. Once the cells become cancerous, they become rounded skin tumors that can be flat or raise and then becomes visibly red or swollen. This type of cancer can spread, which means cells multiplying at an alarming rate, which once the squamous cell carcinoma has spread beyond the skin, though, less than half of people live five years, even with aggressive treatment. Which concludes that it is greatly important to get the cancer treated early before it spreads beyond the skin. This study could possibility be a good direction into leading to better treatments for cancer patients of squamous cell carcinomas.
Citation
Sun, J., Shen, R., Schrock, M., Liu, J., Pan, X., Quimby, D., Zanesi, N., Druck, T., Fong, L. and Huebner, K. (2016). Reduction in squamous cell carcinomas in mouse skin by dietary zinc supplementation. Cancer Medicine, 5(8), pp.2032-2042.