Chang et al. [21] reported that the treatment of immunodeficiency and healthy mice with 500 and 1500 μg/mL arecoline N-oxide, respectively, increased the expression levels of caspase-8 and γ-H2AX in the sublingual hyperplastic lesions of the mice; moreover, substantially elevated (compared with the levels in healthy oral tissues) expression levels of proliferation proteins (Ki67 and proliferating cell nuclear antigen (PCNA)) were observed in the hyperplastic tissues. This evidence concerns the gene CASP8 and immune system disorder.