H2AX and immune system disorder: 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.