**2. Contribution of environmental constituents in mutation**

Throughout the world, skin melanoma is the 19th most widespread cancer. Usually, almost all types of skin cancers are related to environmental factors including contact with immense ultraviolet radiation or due to sun exposure. Environmental mutagens may be synthetic or natural agents in nature [74, 113–116]. these mutagens produce genetic mutations or expand mutational activities during the life span [117, 118]. Most of the environmental mutagens possess genotoxic effects on the next generation via germ cells and continue in the inherent form.

Besides ultraviolet radiation, other radioactive, heavy metals, organic solvents or chemicals, viruses, bacteria, etc. also perform a role to cause cell damage [119–122]. Even, consumption of cigarette smoke, dietary contaminants including mycotoxin, aflatoxin B1, fat consumption, and unorganized stress are themselves integral environmental factors that contribute to cytokeratin disruptions [123]. All these agents are come in contact with the human through directly via skin & lungs or by ingestion. From this channel, these circulate in the body (blood, lymph glands, muscles, bones, tissues, and organs) and initiate mutations. In mutagenesis, these all mutagens penetrate directly to cellular and nuclear membranes and damage DNA by cross-linking (chemically gluing) two bases together. Sometimes, Mutagenesis is also caused by aberrant DNA methylation (epigenetic change) at the genomic level and post-translational modifications at the protein level. Finally, this results in genetic deficiencies cause.
