Mouse skin system

For example, 7,12-dimethylbenz[a]anthracene is a particularly potent carcinogen for the mammary gland of young female Sprague-Dawley rats after oral or intravenous administration (25,26), dietary benzo[a]pyrene leads to leukemia, lung adenoma and stomach tumors in mice (27), and either of these hydrocarbons can induce hepatomas in male mice when injected on the first day of life (28). Nevertheless, the mouse skin system has proved to be particularly valuable because of the rapidity of tumor induction, the ease of detection of tumors and because the multi-stage nature of the carcinogenic process was experimentally established in this system. 

The mechanisms involved in progression in the mouse skin system are unclear. The carcinogens, ENU and MNNG, and the peroxides are all genotoxic compounds. Chromosomal studies have shown that squamous cell carcinomas are highly aneuploid lesions often exhibiting hyperdiploid stem cell lines (42). 

In the newborn mouse system (Table II), the (+) anti dihydrodiol epoxide is clearly more effective than benzo[ajpyrene but this is not the case in initiation-promotion studies or in complete carcinogenesis studies on mouse skin. Nevertheless, there is always... 

In BA metabolism, the procarcinogenic BA trans-3.4-dihydrodiol (26) constitutes 1.5-4% of all the metabolites formed by rat liver microsomes (27) and a major component of the free dihydrodiols formed by mouse skin maintained in short-term organ culture (28). In this system (28). the noncarcinogenic dihydrodiols may be preferentially removed by conjugation reactions to yield water soluble products. 

In addition to this major adduct which, in some biological systems, such as human bronchus (90) or mouse skin (74) or fibroblast 10T1/2 cells in culture (133), accounts for almost all of the DNA adducts, other derivatives have been detected in many systems which have been investigated. These may vary with respect to tissue (134.135.136) or time of exposure (135,137). 

With regard to surface molecule expression of keratinocytes and their role in immunoregulation, a recent study by Loser et al. [49] showed that the member of the TNF superfamily, RANKL, is expressed on keratinocytes of inflamed human and mouse skin. In a murine system, RANKL overexpression in keratinocytes resulted in functional alterations of epidermal dendritic cells and systemic... 

Chloroform can also permeate the stratum comeum of rabbit skin (Torkelson et al. 1976) and mouse skin (Tsuruta 1975). Percutaneous absorption of chloroform across mouse skin was calculated to be approximately 38 pg/min/cm, indicating that the dermal absorption of chloroform occurs fairly rapidly in mice. No reliable studies report the percutaneous absorption of chloroform in humans however, a few clinical reports indicate that chloroform is used as a vehicle for drug delivery (King 1993). Islam et al. (1995) investigated the fate of topically applied chloroform in male hairless rats. For exposures under 4 minutes, chloroform-laden water was applied to shaved back skin for exposures of 4-30 minutes, rats were submerged in baths containing chloroform-laden water. Selected skin areas were tape-stripped a various number of times after various delay periods. It appeared that there was an incremental build-up of ehloroform in the skin over the first four minutes. When compared to uptake measured by bath concentration differences, approximately 88% of lost chloroform was not accounted for in the stratum comeum and was assumed to be systemically absorbed. 

The in vitro diffusion studies for each sample were carried out by using the Franz diffusion cells with a diffusional area of about 1.76cm2. The acceptor compartment of the apparatus was filled with the buffer solution pH 6, USP [21], and maintained at 37 0.5°C via a circulating water system. The diffusion membrane (the cellulose membrane with a molecular weight cut-off point of 1000 or the hairless mouse skin) previously prepared was placed between die donor and the acceptor compartments of the assembly. An accurately weighed 4g of sample was then placed in the donor cell and the diffusion process was started. The solution in the acceptor compartment was continuously stirred with a small magnetic stirrer to maintain the sink conditions. Aliquots from the receptor cells were removed at 0.5,2,4, 8 and 24 h time intervals and replaced with equal... 

Berry DL, Slaga TJ, DiGiovarmi J, et al. 1979. Studies with chlorinated dibenzo-(p)-dioxins, polybrominated biphenyls, and polychlorinated biphenyls in a two-stage system of mouse skin tumorigenesis Potent anticarcinogenic effects. Ann N Y Acad Sci 320 405-414. 

Jadoul and Preat [56] have also proposed a similar explanation for the lack of synergistic effects on transdermal delivery of domperidone with combined electroporation (1 pulse of 1000 V with a time constant of 4 ms) and iontophoresis (0.4 mA/cm2) despite the fact that iontophoresis was switched on within a few seconds after electroporation. Combined pulsing and iontophoresis also did not improve penetration of sodium nonivamide acetate through nude mouse skin [51], Therefore, when combing the two protocols, it should be more efficient to use a system that delivers current during or immediately after pulsing without delay. 

Polysaccharides and generally carbohydrates represent the main carbon sink in the plant cell. Polysaccharides commonly serve nutritional (e.g., starch) and structural (e.g., cellulose) functions in plants. Some polysaccharides are cytotoxic against certain types of cancer, such as mouse skin cancer, or tumor lines in vitro (e.g., mouse Sarcoma-180). However, most polysaccharides exert their action through stimulation of the immune system (cancer immunotherapy). Plants containing polysaccharides with anticancer properties include the following ... 

DiGiovanni J, Viaje A, Berry DL, et al. 1977. Tumor-initiating ability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and Arochlor 1254 in the two-stage system of mouse skin carcinogenesis. Bull Environ Contam Toxicol 18 552-556. 

In contrast, we did not find these concentration-dependent qualitative changes when activation occurred in intact cellular systems (16). We examined the adducts formed in mouse embryo cells in culture and in mouse skin ijri vivo over 40- and 100-fold DMBA concentration ranges, respectively, and found quantitative, but no qualitative, changes in binding (16). At all concentrations, activation appeared to be through the bay region dihydrodiol epoxide pathway. The cellular systems are physically very different from the homogenate systems and it is difficult to... 

---