Ultraviolet Radiation-Induced Impairment of Tumor Rejection Is Enhanced in Xeroderma Pigmentosum A Gene-Deficient Mice

Abstract

Xeroderma pigmentosum (XP)A gene-deficient mice display dermatologic abnormalities similar to human XP, such as enhanced ultraviolet (UV)-induced acute inflammation and high incidence of UVB-induced skin cancer. We have previously reported that UVB-induced immunosuppression of contact hypersensitivity was greatly enhanced in XPA mice. In the present study, we examined the effects of UVB radiation on tumor rejection in XPA mice. Tumor cells established from UVB-induced squamous cell carcinoma in XPA mice were injected subcutaneously. No difference in the development of tumors was observed between the non-irradiated XPA and wild-type mice. Tumors developed, grew in size, and reached the maximum at 7-10 d after the inoculation. Thereafter, all tumors decreased in size and were completely rejected by 4 wk in both strains of mice. When tumor cells were inoculated into the skin that had been irradiated with 50-150 mJ per cm2 of UVB, tumor grew in 60% (12 of 20) of the XPA mice, but only in 4% (one of 23) of wild-type mice. Phenotyping of tumor-infiltrating cells revealed that the migration of natural killer cells and CD8+ T cells was inhibited in UVB-irradiated XPA mice. These data suggest that enhanced UVB-induced impairment of tumor rejection could be partially involved in the cancer development of XP patients.

CXCL1 Inhibition Regulates UVB-Induced Skin Inflammation and Tumorigenesis in Xpa-Deficient Mice

“…In the former case, initial DNA damage by 7,12dimethylbenz[a]anthracene followed by inflammation by 12-O-tetradecanoylphorbol-13-acetate contributes to the development of cancer, whereas in the latter case, UVB causes the failure of immune surveillance in addition to the initial DNA damage and continual inflammation (Abel et al, 2009;DiGiovanni, 1992;Nishigori et al, 1996). However, the dose causing tumor rejection in Xpa-deficient mice was 0.75 kJ/m 2 , which is much larger than the dose in our study, and it also induced inflammation (Miyauchi-Hashimoto et al, 2005). On the other hand, 7,12-dimethylbenz[a] anthracene induced immune suppression as well as inflammation at the same concentration (Miyauchi-Hashimoto et al, 2001).…”

Effects of topical application ofAstragalus membranaceuson allergic dermatitis

“…(1) Patients with AD usually have a personal or familial history of other atopic diseases. (2) Population studies have suggested that AD affects 10-20% of all children in most countries at some time during childhood. (3) Moreover, AD is a multifactorial disease, and its pathogenesis and etiology are not fully understood.…”

“…(3) Moreover, AD is a multifactorial disease, and its pathogenesis and etiology are not fully understood. (2) AD is treated using steroids, antihistamines, immunosuppressive agents, and other medications. However, many studies have indicated that long-term use or even abuse of these agents may cause various side effects.…”

Immune Relevant and Immune Deficient Mice: Options and Opportunities in Translational Research

“…Immunosuppressed contact hypersensitivity (Xpa deficient mice); inhibited intra-tumor migration of NKs and CD8+ T cells (Xpa deficient mice); depressed delayed hypersensitivity in immunized mice; enhanced contact hypersensitivity and skin graft rejection in mice with dermal Langerin+ DCs. [248][249][250][251][252][253][254] Narrowband (NB)-UVB: increased intestinal Tregs, and decreased severity of inflammatory lesions in mouse models of allogeneic GVHD.…”