title: Studying skin tumourigenesis and progression in immunocompetent hairless SKH1-hr mice using chronic 7,12-dimethylbenz(a)anthracene topical applications to develop a useful experimental skin cancer model.
abstract: Previous studies have established that 7,12-dimethylbenz(a)anthracene (DMBA) can initiate skin tumourigenesis in conventional furred mouse models by acting on hair follicle stem cells. However, further cancer progression depends on repeated applications of tumour promoter agents. This study evaluated the timeline involved in skin tumourigenesis and progression in immunocompetent hairless SKH1-hr mice with dysfunctional hair follicles using only DMBA with no additional tumour promoter agents. The results showed that topical application of 30 µg (117 nmol) of DMBA over the back and flank regions of the mouse once a week and 15 µg (58.5 nmol) twice a week produced skin tumours after 7-8 weeks. However, by week 14 a heavy benign tumour load required the mice to be euthanized. Lowering the DMBA dose to 15 µg (58.5 nmol) once a week produced tumours more slowly and allowed the mice to be studied for a longer period to week 23. This low-dose DMBA regimen yielded a high percentage of malignant tumours (58.8%) after 23 weekly applications. Additionally DMBA-treated skin showed an increase in mean epidermal thickness in comparison to untreated and acetone-treated skin. Despite the aberrant hair follicles in SKH1-hr mice, this chemically driven skin cancer model in hairless mice can serve as a suitable alternative to the ultraviolet-induced skin cancer models and can be reliably replicated as demonstrated by both the pilot and main experiments.
authors.affiliation: 1 Department of Biomedical Engineering and Physics, Academic Medical Centre, Amsterdam, The Netherlands.|2 Centre for Optical Diagnostics and Therapy, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Giju
authors.initials: G
authors.lastname: Thomas
authors.affiliation: 3 Department of Plastic and Reconstructive Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Tuk
authors.affiliation: 4 Department of Experimental Animal Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Ji-Ying
authors.initials: JY
authors.lastname: Song
authors.affiliation: 5 Department of Molecular Biophysics, Utrecht University, Utrecht, The Netherlands.
authors.forename: Hoa
authors.initials: H
authors.lastname: Truong
authors.affiliation: 5 Department of Molecular Biophysics, Utrecht University, Utrecht, The Netherlands.
authors.forename: Hans C
authors.initials: HC
authors.lastname: Gerritsen
authors.affiliation: 6 Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Frank R
authors.initials: FR
authors.lastname: de Gruijl
authors.affiliation: 1 Department of Biomedical Engineering and Physics, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Henricus J C M
authors.initials: HJ
authors.lastname: Sterenborg
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000494:pharmacology*; D000287:Administration, Topical; D000818:Animals; D063646:Carcinogenesis / Q000139:chemically induced*; D002273:Carcinogens / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D012878:Skin Neoplasms / Q000139:chemically induced*
chemical_list: D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene
keywords: DMBA; chemical carcinogenesis; cutaneous squamous cell carcinoma; hairless mice; skin cancer models