| First Author | Kemp CJ | Year | 1999 |
| Journal | Carcinogenesis | Volume | 20 |
| Issue | 11 | Pages | 2051-6 |
| PubMed ID | 10545405 | Mgi Jnum | J:58425 |
| Mgi Id | MGI:1347653 | Doi | 10.1093/carcin/20.11.2051 |
| Citation | Kemp CJ, et al. (1999) Resistance to skin tumorigenesis in DNAPK-deficient SCID mice is not due to immunodeficiency but results from hypersensitivity to TPA-induced apoptosis. Carcinogenesis 20(11):2051-6 |
| abstractText | Scid/scid mice have a mutation in the gene encoding the catalytic subunit of DNA-dependent protein kinase (DNAPK(cs)) and are defective in end joining of DNA double-strand breaks. As a consequence, they are radiosensitive, lack mature T and B lymphocytes and are predisposed to lymphomagenesis. To determine if this DNA repair defect also increased predisposition to skin tumor formation, we treated the dorsal skin of scid/scid mice with the carcinogen 7,12-dimethylbenz[a]anthracene followed by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Contrary to expectations, we observed a 5-fold reduction in skin tumor multiplicity in scid/scid mice. We addressed whether this was related to their immunodeficiency by similarly treating Rag1(-/-) and Rag2(-/-) knockout mice which also lack mature T and B lymphocytes. We observed no difference in skin tumor multiplicity for either strain compared with control littermates. This indicates a lack of a significant role for T or B lymphocyte mediated immunity on either papilloma or carcinoma formation. We observed a significant increase in apoptotic and necrotic cell death in follicular and interfollicular epithelial cells of scid/scid mice following TPA treatment. This hypersensitivity of SCID (severe combined immunodeficient) cells to TPA indicates that the resistance to skin tumor formation in scid/scid mice is due to loss of initiated cells through TPA-induced cell killing. |
