Mouse skin, tumor initiating activity

Nesnow, S., Triplett, L. L., and Slaga, T. J. (1983). Mouse skin tumor initiation-promotion and complete carcinogenesis bioassays Mechanisms and biological activities of emission samples. Environ Health Perspect 47, 255-268. 

Benzo(c)phenanthrene (BcP) is exceptionally weak or inactive as a carcinogen in experimental animals (51). On the other hand, the bay region anti diol epoxide of BcP (14) exhibits high tumor initiating activity on mouse skin (65). 

Benzo(b)-, benzo(k)-, and benzo(j)fluoranthene are common environmental contaminants (38). The tumor-initiating activity of benzo-(b)fluoranthene on mouse skin is about equal to that of DBA (38). All three isomers are mutagenic in the Ames assay (110). Syntheses of the 1,2-, 9,10-, and 11,12-dihydrodiols of benzo(b)fluoranthene by Method I have been reported (111,112). 

Table II. Tumor Initiating Activity of 5-MeC Metabolites on Mouse Skin...

Cavalieri, E. L., E. G. Rogan, S. Higginbotham, P. Cremonesi, and S. Salmasi, Tumor-Initiating Activity in Mouse Skin and Carcinogenicity in Rat Mammary Gland of Dibenzo[a]pyrenes The Very Potent Environmental Carcinogen Dibenzo[a,/]pyrene, J. Cancer Res. Clin. Oncol., 115, 67-72(1989). 

Levin W, Wood AW, Chang RL, Kumar S, Yagi H, Jerina DM, Lehr RE, Conney AH (1983) Tumor-initiating activity of benz[c] acridines and twelve of its derivatives on mouse skin. Cancer Res 43 4625-4628... 

Studies on the consequences of stereoselective PAH metabolism in respect to mutagenicity and carcinogenicity were also shown to be strongly dependent on the relative and absolute configuration of the PAH metabolite (Conney, 1982 Thakker et al., 1982). For example, (-)-7R,8R-dihydrodiol benzo[a]pyrene has a 10-foId higher tumor-initiating activity in female CD-I mouse skin than the (+)-7S,8S-enantiomer, and it produces... 

In a dermal initiation/promotion assay, groups of 20 female CD-I mice were administered 10 dermal applications of benzo[b]fluoranthene at total doses of 0,1, and 4 jmol (initiating dose), followed 10 days later by thrice weekly applications of the promoter TPA for a total of 20 weeks (Weyand et al. 1991). Benzo[b]fluoranthene was active as a skin tumor initiator the number of tumors per tumor-bearing mouse (8.5) and the percentage of tumor-bearing mice (100%) were significantly greater than in acetone controls and were increased in a dose-related manner. 

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. 

Higginbotham S, RamaKrishana NVS, Lohansson SL, et al. 1993. Tumor-initiating activity and carcinogenicity of dibenzo(a,/)pyrene versus 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene at low doses in mouse skin. Carcinogenesis 14(5) 875-878. 

LaVoie EJ, Cai Z-W, Meegalla RL, et al. 1993a. Evaluation ofthe tumor-initiating activity of 4-, 5-6-, and 7-fluorobenzo[b]fluoranthene in mouse skin. Chem Bio Interact 89 129-139. 

LaVoie EJ, He Z-M, Meegalla RL, et al. 1993b. Exceptional tumor-initiating activity of 4-fluorobenzo[j]fluoroanthene on mouse skin comparison with benzo[j]fluoranthene, 10-fluoro-benzo[j]fluoranthene, benzo[a]pyrene, dibenzo[a,1]pyrene and 7,12-dimethylbenz[a]anthracene. Cancer Lett 70 7-14. 

Rice JE, Hosted TJ, DeFloria MC, et al. 1986. Tumor-initiating activity of major in-vivo metabolites of indeno-1 2 3 -cd-pyrene on mouse skin. Carcinogenesis 7(10) 1761-1764. 

Siebert D, Marquardt H, Friesel H, et al. 1981. Polycyclic aromatic hydrocarbons and possible metabolites Convetogenic activity in yeast and tumor initiating activity in mouse skin. J Cancer Res Clin Oncol 102 127-139. 

Abies sachalinensis (C.F.Schmidt) Mast, (bark) Spirobiflavonoids (abiesinols). All compounds exhibited potent inhibitory effects on ( )-(iI)-methyl-2-[( )-hydroxyimino]-5-nitro-6-methoxyhex-3-enamide (NOR 1) activation. A spirobiflavonoid showed remarkable anti-tumor-initiating activity in the in vivo two-stage mouse skin carcinogenesis test using peroxynitrite (ONOO PN) as the initiator and 12-O-tetradecanoyl-phorbol- 13-acetate (TPA) as the promoter. Wada et al., 2010[476]. 

J., Sukumaran, K.B., and Harvey, R.G. (1979) Potent tumor initiating activity of the 3,4-dihydrodiol of 7,12-dimethylbenz[a]anthracene in mouse skin. Cancer Res., 39,... 

JP-8 has not been tested for tumor-initiating or -promoting activity. Jet fuel A has been tested for tumor promoting activity in the CD-I mouse model of skin tumors initiated by dimethylbenzanthracene (DMBA) (Nessel et al. 1999). Other MDFs have been tested for tumor-promoting activity in the same model system. In addition, hydrodesulfurized kerosene, hydrodesulfur-ized middle distillates, and lightly refined paraffinic oil have been tested for initiating activity with the model. Those studies are briefly described below. 

PTX (1) also caused a significant reduction in the actin cytoskeleton as with other polyol and polyether toxins such as pectenotoxin-6 and maitotoxin [33]. Thus, the cytoskeleton is suggested to be an early target for the toxic effect of such toxins. Furthermore, the skin tumor promoter activity of palytoxin has gathered attention. Notably, palytoxin did not activate protein kinase C but extracellular signal-regulated kinase (ERK) through a mechanism that involves inactivation of an ERK phosphatase in keratinocytes derived from initiated mouse skin [34]. 

Takahashi, M. (2007) Kojic acid-absence of tumor-initiating activity in rat liver, and of carcinogenic and phoo-genotoxic potential in mouse skin. /, Toxicol Sci, Vol.32(2), pp.143-159. 

Tumor Initiation in Mouse Skin Metabolite Activity/Activity of BP at Same Dose... 

Tumor Initiation in Mouse Skin Metabolite Activity/Activity of BP at Same Dose Lung Adenoma Induction in Newborn Mice Metabolite Activity/Activity of BP at Same Dose ... 

Methylphenanthrene fulfills the structural requirements but, as in the case of the other monomethylphenanthracenes, is inactive as a tumor initiator on mouse skin ( 5). This seems to be due to facile metabolic detoxification by formation of the 9,10-dihydrodiol, a process which is blocked in the tumorigenic isomers 1,4- and 4,10-dime thy lphenanthrene ( 5,j>). Among the methylated benzoicIphenan-threnes, the 3-,4-,5-, and 6-methyl isomers are the most tumori-genic The 1-methyl isomer, in which the methyl group is present in a 4-sided "fjord , is only weakly active like the parent hydrocarbon (23). 

Slaga, T.J., W.M. Bracken, A. Viaje, D.L. Berry, S.M. Fischer, D.R. Miller, W. Levin, A.H. Conney, H. Yagi, and D.M. Jerina. 1978. Tumor initiating and promoting activities of various benzo[a]pyrene metabolites in mouse skin. Pages 371-382 in P.W. Jones and R.I. Freudenthal (eds.). Carcinogenesis a Comprehensive Survey. Vol. 3. Polynuclear Aromatic Hydrocarbons Second International Symposium on Analysis, Chemistry, and Biology. Raven Press, NY. 

---