Mouse skin painting

Grimmer G et al Characterization of polycyclic aromatic hydrocarbons as essential carcinogenic constituents of coal combustion and automobile exhaust using mouse-skin-painting as a carcinogen-specific detector. Toxicol Environ Chem 6 97, 1983... 

Chasey KL, McKee RH. 1993. Evaluation of the dermal carcinogenicity of lubricant base oils by the mouse skin painting bioassay and other proposed methods. J Appl Toxicol 13(l) 57-65. 

Freeman et al. (1993) tested jet fuel A in the C3H mouse skin-painting model, using two treatment protocols. In the first protocol, jet fuel A was applied neat twice a week to the skin of C3H mice for 2 yr. In the second... 

As summarized by Nessel (1 999), middle distillate fractions (MDFs) have been tested in numerous lifetime mouse skin-painting studies over the last 20 yr. Early mouse skin-painting studies documenting the carcinogenicity of MDFs in mouse skin include those of Lewis et al. (1984) and Biles et al. (1988), as cited by Nessel (1999). MD API 81 -07, a hydrodesulfurized kerosene, was also shown to induce skin tumors in a C3H/HeJ mouse skin-painting 2-yr bioassay in 50% of the animals with a tumor latency of 76 wk (API 1988, as cited by Skisak 1991). 

An MDF known as lightly refined paraffinic oil was tested in the C3FI mouse skin-painting model, applied neat and in 25% and 50% dilutions in mineral oil or in toluene (Freeman et al. 1993). The neat lightly refined paraffinic oil induced tumors in 8% of the treated mice no tumors were observed in animals that received the diluted material. Skin irritation was observed in animals that received either the neat material or material diluted in toluene but not in animals that received material diluted in mineral oil. 

The role of skin irritation in the development of skin tumors was investigated by Nessel et al. (1998). In lifetime C3F1 mouse skin-painting studies, MDFs, including a straight-run kerosene, were applied neat and in 50% and 28.6% dilutions. Treatment with the neat straight-run kerosene induced skin tumors and skin irritation treatment with the diluted material produced neither... 

Earlier, Wynder and Wright (4354) had reported that the slight tumorigenicity observed with an alkane fraction of tobacco smoke condensate in a mouse skin-painting bioassay was due not to the alkanes per se but to trace amounts of PAHs in the alkane fraction. 

Consideration of all the tumorigenic PAHs and their levels in CSC could account for no more than 3% of the observed biological activity in mouse skin-painting studies. In 1961, Wynder and Hoffmann (4312) stated ... 

In 1959, unable to explain the bioassay (mouse skin-painting) results with CSC on the basis of either its B[a]P content (less than 2% explainable) or its total PAH content (less than 3% explainable), Wynder and Hoffmann (4307) at the 1959 American Association for Cancer Research (AACR) meeting added the concept of promotion by low molecular weight phenols to the concept of tumor initiation by PAHs in an attempt (unsuccessful) to explain the bioassay results. They reiterated their view the following year at the 1960 AACR conference (4309) The phenol fraction could be established as an important promoting portion of the tobacco smoke condensate. ... 

On several occasions, the U.S. Surgeon General in his periodic reports on smoking and health discussed the relationship between the levels of PAHs in cigarette smoke, their tumorigenic potency to mouse skin, and the observed biological response with CSC in mouse skin-painting bioassays. 

The results of a number of such assays [mouse skin-painting] present a puzzling anomaly the total tar from cigarettes has about 40 times the carcinogenic potency of the benzo(a) pyrene present in the tar. The other carcinogens known... 

The results of a number of such assays [mouse skin-painting] present a puzzling anomaly the total tar from cigarettes has about 40 times the carcinogenic potency of the benzo(a) pyrene present in the tar. The other carcinogens known to be present in tobacco smoke are, with the exception of dibenzo(a,i)pyrene, much less potent than benzo(a)pyrene and they are present in smaller amonnts. Apparently, therefore, the whole is greater than the snm of the known parts, [see p. 58 in (3999)]... 

The coupling of the findings reported by Boutwell et al. (414) on the promoting effects of low molecular weight phenols on PAHs in the mouse skin-painting bioassay with the failure to explain the tumorigenicity of CSC on the basis of its PAH content subsequently triggered extensive research both within and outside of the tobacco industry on several aspects of the phenols in tobacco smoke. 

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 the controversy over the biological properties of the phenols in tobacco smoke, that is, were they promoters of the tumorigenicity of the PAHs in the mouse skin-painting bioassay or cocarcinogens for the PAHs in that bioassay Or were they noncontributors or minor contributors to the bioassay results The next step after identification, refinement of quantitation procedures, and resolution of the question of precursors was the determination of which cigarette design parameters would permit control of the levels of phenols in MSS. 

This suggestion, coupled with the mouse skin-painting bioassay results reported by Takizawa (3865a) that several simple quinones such as 2,5-cyclohexadiene-l,4-dione (p-benzoquinone), 1,2-naphthalenedione (1,2-naphthoquinone), and 1,4-naphthalenedione (1,4-naphthoquinone) were tumorigenic to mouse skin, raised serious questions about the desirability of adding phenols to the tobacco blend to enhance the odor and flavor of its smoke. Despite the many studies in which benzene was used as the solvent for testing of the tumorigenicity of PAHs, benzene seldom induced tumors in... 

The mouse skin-painting bioassay results with 2,5-cyclo-hexadiene-l,4-dione (p-benzoquinone) were subsequently confirmed by Tiedemann (3916a). Neither of the higher molecular weight tricyclic quinones 9,10-anthracenedione (9,10-anthraquinone) (3865a) or 9,10-phenanthrenedione (9, 10-phenanthrenequinone) (3865a) was reported to be tumorigenic to mouse skin. 

In the early days of the studies on the specific tumorigenicity of various classes of compounds to mouse skin, investigators were intrigued by the activities exhibited by aromatic hydrocarbons, their dihydric phenols, and the quinones corresponding to the dihydric phenols. The results of mouse skin-painting bioassays with various aromatic hydrocarbons ranging in complexity from monocyclic to hexacyclic, their dihydric phenols, and the corresponding quinones are summarized in Table IX.B-1. 

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