The tyrosinase (Tyr) gene encodes the enzyme tyrosinase that catalyses the 
conversion of L-tyrosine into DOPA (3,4-dihydroxyphenylalanine)-quinone. The 
albino mutation abrogates functional activity of tyrosinase resulting in 
deficiency of melanin pigment production in skin and retina. Tyr maps to a 
region in the central position of Chromosome 7 that contains a skin 
tumor-modifier locus. We rescued the albino mutation in transgenic mice to 
assess a possible role of Tyr gene in two-stage skin carcinogenesis. Transgenic 
expression of the functional Tyr(Cys) allele in albino mice (Tyr(Ser)) caused a 
reduction in skin papilloma multiplicity, in four independent experiments and at 
three dose levels of DMBA (9,10-dimethyl-1,2-benzanthracene). In vitro 
mechanistic studies demonstrated that transfection of the Tyr(Cys) allele in a 
human squamous cell carcinoma cell line (NCI-H520) increases tyrosinase enzyme 
activity and confers resistance to hydrogen peroxide-induced oxidative DNA 
damage. These results provide direct evidence that the Tyr gene can act as a 
skin cancer-modifier gene, whose mechanism of action may involve modulation of 
oxidative DNA damage.