Mouse skin experiments

Experiments on the metabolic activation of 5-MeC in mouse skin are in agreement with the pivotal role of anti-DE-I in expressing its tumorigenicity. The major DNA adduct formed in mouse skin treated with pH]5-MeC has the structure indicated in Figure 5, resulting from addition of the exocyclic amino group of deoxyguanosine to car-... 

The carcinogenicity of a series of PAH in the mammary gland has been examined in 50-day-old female Sprague-Dawley rats using direct application of the compound to the mammary tissue (1 , 17, 18). The results of these experiments, presented in Table III, are compared to the carcinogenicity results in mouse skin from repeated application obtained in our laboratory and others. PAH were selected because they were or were not expected to be activated by one-electron oxidation, based on the hypothesis that compounds with relatively high IP cannot be activated by this mechanism. Furthermore, some... 

Table 6—Effect of DMSO on the permeability of propranolol hydrochloride from Methocel matrix diffusion experiment through hairless mouse skin...

Figs. (10) and (11). Inhibition by monism (3) of tumor promotion by teleocidin in a two-stage carcinogenesis experiment on mouse skin. Inhibition was achieved by a single application of 100 pg of DMBA, and teleocidin (2.5 pg) and morusin (1 mg) were applied twice a week throughout the experiments. 

Thermal dependence of the flux of the four permeants (butanol, octanol, hydrocortisone and ARA-A) showed the three more lipophilic molecules exhibited large increases in permeability as the temperature of hairless mouse skin was raised from about 10 to 70°C. In contrast, no further enhancement of hydrocortisone flux was noted at temperatures above approximately 70°C. However, the less lipophilic solute, ARA-A, did not experience significant enhancement in permeability until higher termperatures above 37°C. Permeation of the molecules was either beginning to occur by alternate pathways or coming under dermis control. 

Further insightful observations concerning the mechanistic role of OA were provided by a series of experiments in which the flux of piroxicam (an anionic antiinflammatory agent) across OA-treated hairless mouse skin was... 

Carcinogenicity experiments on mouse skin were conducted with groups of 20 female CD-I mice. Benzo[a]pyrene (0.05 mg) dissolved in 50 mL toluene was applied to shaved skin of mice twice weekly for 6 months (Warshawsky et al. 1993). Tumor incidence was determined at the end ofthe study. Benzo[a]pyrene produced no tumors. 

Several experiments have shown that most PAH mixtures are considerably less potent than individual PAHs. Various combustion emissions and benzo[a]pyrene have been examined for carcinogenic potency and tumor initiation activity on mouse skin. In all cases, PAH mixtures were much less potent than benzo[a]pyrene. The authors calculated relative potency estimates that ranged from 0.007 for coke oven emissions extract to less than 0.002 for diesel engine exhaust extract, using papillomas per mouse per milligram of the mixture as the end point (Slaga et al. 

Figure 6.8. A series of experiments using the mouse skin model that demonstrated the concepts of initiation and promotion adapted from Pitot (1986).

FIG. 9 Experimental concentration profile of hydroquinone (HQ) above a hair follicle in hairless mouse skin. The experiment corresponds to diffusion of HQ through the hair follicle. (Donor solution 0.2 M HQ and 0.2 M NaCl receptor solution 0.2 M NaCl.) The solid fine corresponds to the best fit of Eq. (10) to the data. (From Ref. 27.)... 

Studies with B[a]P and the C31 and C35 saturated hydrocarbons (SHC), where the SHC B[a]P ratio was 200 1 and 100 1, showed that both saturated hydrocarbons exerted a significant inhibiting effect at both levels on the specific tumorigenicity of B[fl]P in mouse skin-painting experiments [4311,4314, see also pp. 330-331 in (4319) and pp. 370-371 in (4332)]. 

Van Duuren et al. also noted that rutin, a tobacco component, also inhibited B[a]P carcinogenesis in the mouse skin-painting bioassay. From the results of their biological experiments on cocarcinogenesis (simultaneous and repeated application of an agent, in this case 1,2-benzenediol [catechol]), with B[fl]P, Van Duuren et al. (4029) deduced that 1,2-benzenediol (catechol) showed remarkable cocarcinogenic activity with B[fl]P. They reported ... 

Despite numerous statements to the contrary—that the data from mouse skin-painting experiments with CSC were not extrapolable from mouse skin to the human lung, some authorities continued to imply that such data were meaningful... 

Volatile NNA tumorigenicity in laboratory animals was repeatedly cited with the implication that this property was extrapolable to man because of cigarette smoke NNAs. In laboratory animals, NNAs are organ-specific tumorigens and seldom have been shown to induce carcinoma at the painting site in mouse skin-painting experiments. Hoffmaim and Wynder (15A29) noted ... 

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