Skin papillomas

Bums, F.J., Vanderlan, M., Snyder, E. and Albert, R.E. (1976). Induction and progression kinetics of mouse skin papillomas. In Slaga, T.J., Sivak, A. And Boutwell, R.K. (Eds). Carcinogenesis, Vol. 2. Modifiers of Chemical Carcinogenesis. Raven Press, New York, pp. 91-96. 

In a 52-week study, mice were exposed 2 times each week to 41.7 or 83.3 mg/kg of phenol in a 5 or 10% solution in benzene (Boutwell and Bosch 1959). Severe skin damage was reported after 36 weeks in the mice exposed to 83.3 mg/kg. Skin papillomas were reported in mice exposed at 41.7 mg/kg. Because phenol was applied in benzene which is also a skin irritant, this study is not presented in Table 2-3. 

Technical-grade CMME (contaminated with BCME), on subcutaneous injection in mice, has produced local sarcomas. Dermal application of mice, followed by a phorbol ester promoter, resulted in an apparent excess of skin papillomas and carcinomas. Inhalation studies in mice showed an equivocally increased occurrence of lung tumors compared with unexposed controls. ... 

Mammary carcinomas and forestomach papillomas were observed in mice after gavage administration. DBA has also been shown to cause skin papillomas and carcinomas in mice when applied dermally 3 times/week for a lifetime.Subcutaneous injection of Ipmol of DBA three times weekly for 20 doses induced injection site sarcomas in 100% of female Sprague-Dawley rats by 33 weeks. ... 

Both D,L- and ero-l,2 3,4-diepoxybutane induced skin papillomas and carcinomas in mice after dermal application. Lung tumors were produced in mice after intraperitoneal administration of 27, 108, or 192mg/kg (total dose). The tumor incidences at these doses were 55%, 64%, and 78%, respectively, compared with 31 % in control mice. ... 

Diglycidyl ether is extremely damaging to skin, producing ecchymoses and necrosis. In one long-term study, skin painting three times per week for 1 year caused hyperkeratosis, epithelial hyperplasia, and skin papillomas. ... 

In long-term animal studies, dimethyl carbamoyl chloride produced local tumors by each of three routes of administration. Two milligrams applied to the skin of mice three times/week for 492 days caused skin papillomas in 40 of 50 animals of these, 30 progressed to skin carcinomas. After weekly subcutaneous injections of 5 mg for 26 weeks, 36 of 50 female... 

Adverse reactions occurring in at least 3% of patients included the following Upper abdominal pain, anxiety, appetite decrease, asthenia, constipation, cough, depression, herpes simplex, influenza, insomnia, myalgia, peripheral neuropathy, pruritus (not otherwise specified), sinusitis, skin papilloma, weight decreased. 

Hexachlorobutadiene did not produce skin papillomas, carcinomas, or tumors at distant sites in mice after application of dose levels of 2-6 mg/mouse for 440-594 days (Van Duuren et al. 1979). Data from this exploratory study are not sufficient to rule out carcinogenic effects via dermal exposure. 

Balmain, A., Ramsden, M., Bowden, G., and Smith, J. (1984). Activation of the mouse cellular Harvey-ras gene in chemically induced benign skin papillomas, Nature 307,658. 

Figure 6.51 Scheme showing the initiation and promotion of skin papillomas and carcinomas after treatment with DMBA and promotion with TPA (Fig. 53). The initiation converts (mutation) proto-oncogene ras to oncogene and promotion stimulates growth and division, forming a papilloma. Further exposure to initiator DMBA, alters (mutation) tumor suppressor gene p53 which collaborates with ras and causes carcinoma formation. See text for full explanation. Abbreviation DMBA, dimethylbenzanthracene. Source From Ref. 15.

D,L-Diepoxybutane and /wcAso-diepoxybutanc induced skin papillomas and squamous-cell carcinomas when applied to the skin of female Swiss mice at a dose of approximately 3 or 10 mg in 100 mg acetone three times per week for life (Van Duuren et al., 1963, 1965). Subcutaneous injection of 0.1 mg D,L-diepoxybutane in 0.05 mL tricaprylin once per week for more than one year induced local fibrosarcomas in female Swiss mice no tumour was observed in three solvent-treated control groups. Similar findings were seen in female Sprague-Dawley rats (Van Duuren et al., 1966). 

Benzal chloride was tested in two experiments in mice by skin application, the results of which were reported together. In the first experiment, the total dose of benzal chloride was about 289 mg per mouse during a 50-wcek dosing period, after which all mice were killed at week 82. No skin tumours developed in 20 controls, while, in the treated group of 19 (14 of which had died by the end of the experiment), nine mice had squamous cell carcinomas of the skin and two had skin fibrosarcomas. In the other experiment in which the total benzal chloride dose was about 1109 mg per mouse, but which was terminated after just 43 weeks, 2/10 mice developed skin papillomas compared with 0/10 in the controls (lARC, 1982). 

Groups of female ICR-Jcl mice were exposed to air or to benzoyl chloride vaporized at 50°C [concentration not stated] for 30 min per day on two days per week for five months. They were then observed for a further seven to nine months (12-14 months total). In the control and exposed groups, respectively, lung tumours were observ ed in 3/30 (3 adenomas) and 3/28 (1 adenoma and 2 adenocarcinomas) mice and skin papillomas in 0/30 and 2/28 mice. The differences in incidence were not significant (Yoshimura et al., 1986). [The Working Group noted the short duration of exposure and observation time, allowing only comparison with mice simultaneously exposed to benzotrichloride.]... 

Mouse-. Groups of five male TGAC or FVB/N non-carrier mice, six to seven weeks of age, were administered 3 mg phenol (reagent grade) per animal in acetone by skin application twice per week for up to 20 weeks. A skin papilloma occurred in an exposed TGAC mouse, whereas none occurred in controls (not considered to be significant) (Spalding et al., 1993). 

Mouse Groups of 50 male and 50 female B6C3Fi mice, eight weeks of age, were administered skin applications of 0, 88 or 177 mg/kg bw 2,3-dibromo-l-propanol (98% pure) in 95% ethanol on five days per week for 36-39 weeks (males) or 39-42 weeks (females). The study was terminated at 36-39 weeks (males) and 39 2 weeks (females) because sera from sentinel mice housed in the same room as the study animals were found to be positive for antibodies to lymphocytic choriomeningitis virus. As shown in Table 1, increased incidences of skin papillomas, forestomach papillomas and forestomach carcinomas were observed in both sexes. Hepatocellular adenomas were seen in 1/50 control, 2/50 low-dose and 9/50 high-dose p < 0.05) male mice no data for liver were reported in females (Eustis et al., 1995). 

Diisopropyl sulfate was tested for carcinogenicity by subcutaneous injection in one strain of rats and by skin application in one strain of mice. It produced local sarcomas in rats and skin papillomas and carcinomas in mice. In a screening study in two strains of mice, an increased incidence of lung adenomas was obsen ed following subcutaneous injection (lARC, 1992). 

Fig. (5). Inhibitory effect of taraxasterol (239) and faradiol (232) on the promotion of skin papillomas by TPA in DMBA-initiated mice. Starting 1 week after initiation by a single topical application of 50 pg of DMBA, 1 pg of TPA was applied twice weekly. Topical application of 239 (2.0 gmol), 232 (2.0 nmol) and vehicle was performed 30 min before each TPA treatment. Data are expressed as percentage of mice bearing papillomas (A), and as average number of papillomas per mouse (B). = +TPA with vehicle alone O = +TPA with 239 A = +TPA with 232 [85].

Katiyar SK, Mohan RR, Agarwal R, Mukhtar H. 1997. Protection against induction of mouse skin papillomas with low and high risk of conversion to malignancy by green tea polyphenols. Carcinogenesis 18 497-502. 

Cisplatin caused lung adenomas and skin papillomas in female mice and leukemia in rats. Animal carcinogen reasonably anticipated to be a human carcinogen.2... 

TCDD inhibited the development of skin papillomas otherwise initiated by 1,3-dimcthylbenz(o)-anthracene (DMBA) (Berry et al. 1979). In intermediate-duration experiments, 2,3,7,8-TCDD did not promote skin tumors initiated by DMBA (Berry et al. 1978, 1979). In contrast, the promoting ability of... 

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