Table 2.
Country, Year [Reference] | Study Design | Animal Model and Groups | Tissue or Cell Type | UV Radiation Treatment | Methylation Type | Technique | Outcome and Conclusion | Other Outcomes |
---|---|---|---|---|---|---|---|---|
USA, 2003 [42] | Effect of Epigallocatechin-3-gallate (EGCG) on the skin of mice submitted to a UV-induced carcinogenesis protocol | SKH-1 mice divided into 3 groups: non-irradiated (control), irradiated and irradiated + EGCG | Cells from dorsal skin biopsies (papillomas and carcinomas) and epidermal cells from the non-irradiated group | UVB (180 mJ/cm2); irradiation once a day for 10 days (tumor initiation); then 3× a week for 30 weeks (tumor promotion) | Global | IHC | Global hypomethylation and ↓ in DNMT1 activity on both irradiated groups | ECGC prevented global hypomethylation in the treated group |
USA/South Coreia, 2014 [43] | Comparison of methylation profiles from skin tumors submitted to irradiation and DMBA/TPA-induced carcinogenesis | SKH-1 female mice from 7 to 8 weeks of age irradiated and non-irradiated (control) with UVB; CD-1 female mice of 6 weeks of age treated with DMBA/TPA | Cells from biopsies of dorsal skin tumors (papillomas and carcinomas); epidermal cells from the control group | UVB (280–320 nm; 70–80% of total energy); UVA (320–375 nm; 20–75% of the total energy). Mice were exposed to UV light (30 mJ/cm2) twice a week for 36 weeks | Whole-genome | MeDIP-Seq; IPA | Hypermethylation in 4140 genes and hypomethylation in 1863 from the UV group (sequences involved in the molecular mechanism of cancer were the most affected) | DMBA/TPA promoted an altered methylation profile when compared to controls. |
USA, 2017 [44] | Effect of Honokiol (HK) on the skin’ methylation profile of both irradiated and non-irradiated | C3H/HeN female mice (5 to 6 weeks); 129 Ola/C57BL/6 mice, both COX-2 deficient and wild type. Groups were divided in non-irradiated (control), irradiated and irradiated + HK in two different concentrations (4% and 8%) | Skin biopsies from shaved dorsal region | Mice were irradiated with 150 mJ/cm2 of UVB radiation (280–320 nm; ≈ 80% of total energy) for 4 consecutive days and sacrificed 24 h after the last irradiation session | Global | IF; ELISA; Dot-blot analysis | Higher numbers of 5mC-positive cells; ↑ expression of Dnmt1, 3a and 3b, as well as Sp1 and 3; ↓ TET activity; ↑ global methylation levels in irradiated animals when compared to controls | Topical application of HK inhibited the UVB-induced formation of 5-mC-positive cells in a dose-dependent manner |
USA, 2019 [45] | Analysis of methylation profile during different stages of radiation-induced carcinogenesis | SKH1 mice divided into two groups: non-irradiated (control) and submitted to UVB | Epidermal and tumor biopsies from different time points (2, 15 and 25 weeks); whole skin samples from the control group | UVB (60mJ/cm2), twice a week for 25 weeks. | Genome-wide, base resolution | MethylSeq; Pyrosequencing | Changes in 974 DMRs: 50% hypomethylated and 50% hypermethylated; methylation and expression are related in 60% of the DMRs (ex: Cdk4, Tgfbr2, Fgfr1, Bcl2l1, Pik3cb) in the epidermis of irradiated animals. | |
USA, 2019 [46] | Analysis of effect of tripterpenoid ursolic acid (UA) upon the methylation profile of mice submitted to radiation-induced carcinogenesis | SKH-1 hairless mice divided into 3 groups: non-irradiated + acetone (control), irradiated + acetone and irradiated + UA | Epidermal cells from skin samples (control) and skin tumor cells from different time points (2, 15, and 25 weeks) | UVB (60mJ/cm2), twice a week for 25 weeks | Genome-wide, base resolution | MethylSeq; Pyrosequencing | Hypermethylation (Slco5a1, Ogfrl1, Bend6, Mgat4a, Creg2, Gm973, Slc4a3, Arl4c, Mlph, Twist2 Slco5a1, Ogfrl1, Bend6, Mgat4a, Creg2, Gm973, Slc4a3, Arl4c, Mlph, Twist2) and hypomethylation (Npbwr1, Plekhb2,Klf7, Mgat5, Ube2t, Phlda3, Kcnj9, Fbxo5, Plagl1,Myb); altered transcript levels in agreement with methylation analysis in irradiated animals; | Ursolic acid was able to reverse all observed methylation changes. |
IHC: Immunohistochemistry; MeDIP-Seq: Methylated DNA immunoprecipitation sequencing; IPA: Ingenuity® pathway analysis—analysis of function and pathway of methylated genes; IF: Immunofluorescence; ELISA: Enzyme-linked immunosorbent assay; MethylSeq: Methylation sequencing.