desmosine and Skin-Neoplasms

Chronic exposure to sunlight [ultraviolet light B (UVB) irradiation] is the most common cause of non-melanoma skin tumors. In the present study, we investigated the effects of passive cigarette smoke superimposed over UVB irradiation, on tumor development, skin pathology and matrix changes in SKH-1 hairless mice. Groups of mice were exposed to 0.1 J/cm(2) of UVB five times per week for 20 weeks and/or exposure to passive cigarette smoke from 40 cigarettes a day over the same time period. UVB exposure resulted in an average of four large squamous cell carcinomas (SCC) and 15 smaller papillomas per mouse, whereas exposing the mice to both UVB + passive cigarette smoke completely prevented SCC formation and averaged less than one small papilloma per mouse. Oxidative DNA damage was investigated and there were no significant changes in the levels of urinary DNA adducts between control, smoke, UV and UV + smoke groups with the exception of 8-oxo guanine which was significantly reduced in the presence of passive cigarette smoke. Immunohistochemistry results revealed that tumor necrosis factor receptor 2 (TNF-R2), glycogen synthase kinase-3 beta, nuclear factor kappa B (NF-kappaB)/p65, KI-67 and cyclooxygenase 2 (COX-2) were markedly up-regulated in the epithelium by UVB exposure, whereas passive smoke exposure combined with the UVB irradiation completely blocked the expression of these proteins. Our results suggest that passive smoke exposure prevents UVB-induced SCC in mice and dramatically reduces the incidence of non-malignant papillomas by altering the NF-kappaB signalling pathway of tumorigenesis.

Topics: Animals; Dermatitis, Contact; Desmosine; DNA Damage; Female; Immunohistochemistry; Mice; Mice, Hairless; NF-kappa B; Oxidative Stress; Papilloma; Skin; Skin Neoplasms; Tobacco Smoke Pollution; Ultraviolet Rays

Lutein and zeaxanthin are xanthophyll carotenoids with potent antioxidant properties protecting the skin from acute photodamage. This study extended the investigation to chronic photodamage and photocarcinogenesis. Mice received either a lutein/zeaxanthin-supplemented diet or a standard nonsupplemented diet. Dorsal skin of female Skh-1 hairless mice was exposed to UVB radiation with a cumulative dose of 16,000 mJ/cm(2) for photoaging and 30,200 mJ/cm(2) for photocarcinogenesis. Clinical evaluations were performed weekly, and the animals were sacrificed 24 h after the last UVB exposure. For photoaging experiments, skin fold thickness, suprapapillary plate thickness, mast cell counts and dermal desmosine content were evaluated. For photocarcinogenesis, samples of tumors larger than 2 mm were analyzed for histological characterization, hyperproliferation index, tumor multiplicity, total tumor volume and tumor-free survival time. Results of the photoaging experiment revealed that skin fold thickness and number of infiltrating mast cells following UVB irradiation were significantly less in lutein/zeaxanthin-treated mice when compared to irradiated animals fed the standard diet. The results of the photocarcinogenesis experiment were increased tumor-free survival time, reduced tumor multiplicity and total tumor volume in lutein/zeaxanthin-treated mice in comparison with control irradiated animals fed the standard diet. These data demonstrate that dietary lutein/zeaxanthin supplementation protects the skin against UVB-induced photoaging and photocarcinogenesis.

Topics: Animals; Desmosine; Diet; Lutein; Mast Cells; Mice; Mice, Hairless; Skin; Skin Aging; Skin Neoplasms; Tumor Burden; Ultraviolet Rays; Xanthophylls; Zeaxanthins

Elastin from both elastofibroma and control skin samples was analyzed by means of pancreatic elastase digestion and subsequent biochemical studies, such as for elastin content and amino acid composition. Elastin of elastofibroma was more resistant to elastase digestion than that of controls. Elastin content was increased almost twice (wet weight) or three times (dry weight) in elastofibroma. The amino acid composition had the characteristics of elastin; however, the cross-linking amino acids such as desmosine, isodesmosine, and lysinonorleucine were increased in elastofibroma when compared with controls. An electron microscopic study showed that the interspersed cells had prominent intermediate filaments without any periodicity, pinocytotic vesicles, rough endoplasmic reticulum, and other organelles. These cells were considered to be fibroblasts not myofibroblasts. Therefore, it could be supposed that fibroblasts newly form an elastin that has a slightly different amino acid composition from that of controls.

Topics: Aged; Amino Acids; Desmosine; Dipeptides; Elastin; Female; Fibroma; Humans; Isodesmosine; Microscopy, Electron; Pancreas; Pancreatic Elastase; Shoulder; Skin Neoplasms

Biopsies of a cutaneous osteoma and of normal-looking skin from a 1-year-old girl were studied for histological appearance and collagen biochemistry. The mineralized tissue contained a matrix similar to bone: Only type I collagen, with a hydroxylysine content (0.48%) higher than in the skin (0.35%) and dihydroxylysinonorleucine as the major reducible crosslink. As expected, the normal skin adjacent to the lesions contained type I and type III collagen and as major crosslinks hydroxylysinonorleucine and histidinohydroxymerodesmosine. Histological studies showed the presence of woven bone with very little trabeculation. Numerous active osteoblasts were laying down a rapidly calcified non-lamellar matrix. Osteocytes and multinucleated osteoclasts were also noted. The study demonstrates the osseous nature of the lesion and suggests that an abnormal cell differentiation is associated with this form of osteoma.

Topics: Bone and Bones; Collagen; Desmosine; Dipeptides; Female; Histidine; Humans; Hydroxylysine; Infant; Infant, Newborn; Osteoma; Skin Neoplasms

The Buschke-Ollendorff syndrome is an association of cutaneous lesions, dermatofibrosis lenticularis disseminata, with osteopoikilosis. This condition is inherited in an autosomal dominant pattern. In order to clarify the biochemical nature of the skin lesions, we have examined 12 patients with the Buschke-Ollendorf syndrome, representing 2 unrelated kindreds. Histologically, the lesions were characterized by excessive amounts of unusually broad, interlacing elastic fibers in the dermis. Digestion of skin secretions with pancreatic elastase completely removed these fibers. Electron microscopy of the dermis further revealed markedly branched elastic fibers without fragmentation. The accumulation of elastin in the skin was also demonstrated by measurements of desmosine employing a radioimmunoassay. The desmosine content of the skin lesions increased 3- to 7-fold when compared to the skin either from healthy controls or from uninvolved skin adjacent to a lesion. The results indicate that the skin lesions of the Buschke-Ollendorff syndrome are connective tissue nevi of the elastin type. Cell cultures from these patients may provide a convenient model to study the control mechanisms involved in elastin metabolism.

Topics: Desmosine; Elastic Tissue; Elastin; Fibroma; Humans; Osteopoikilosis; Osteosclerosis; Skin; Skin Neoplasms; Syndrome