Mouse skin carcinogenesis test

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]. 

So far, no potential cancer chemopreventive agent constituent from a Hernandia species has been subjected to biological follow up after the initial in vitro investigation, e.g., by using a mouse mammary organ culture assay [75] or a two-stage mouse skin carcinogenesis test [86]. 

Tanaka R, Tokuda H, Ezaki Y (2008) Cancer chemopreventive activity of rosin constituents of Pinus spez. and their derivatives in two-stage mouse skin carcinogenesis test. Phytomedicine 15(ll) 985-992. doi 10.1016/j.phymed.2008.02.020... 

Phenol was tested for carcinogenicity by oral administration in rats in one study and in mice in one study. An increased incidence of leukaemia was reported in male rats treated with the lower dose but not in high-dose rats or in mice or female rats. Phenol was a promoter of mouse skin carcinogenesis in two-stage protocols. 

Further, the two-stage carcinogenesis test of several natural products, which exhibited the inhibitory effects on mouse skin carcinogenesis, on pulmonary tumors (4-nitroquinoline-iV-oxide is as an initiator and glycerol is as a promoter) and on liver carcinoma (iV-nitrosodiethylamine is as an initiator and phenobarbital is as a promoter) were also examined. 

Among the numerous quinoline derivatives known to exist, only a few have been tested for carcinogenicity. Positive results have been obtained with quinoline, 4-nitroquinoline A -oxide, and 4-hydroxyaminoquinoline 1-oxide (26). Dong et al. (17) have recently reported that quinoline may also display some activity as a tumor initiator in the two-stage mouse skin carcinogenesis system. Isoquinoline, however, was reportedly inactive under the same test conditions. 

Soyasapogenol B, soyasaponins I and II and wistariasaponins from Wistaria brachybotrys (wistariasaponin C corresponds to astragaloside VIII) decreased (20-30%) the Epstein-Barr Virus (EBV) activation induced by the tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate) in Raji cells at a concentration of lxlO2 mol ratio [151]. Soyasaponin I from the same plant exhibited remarkable inhibitory effects on mouse skin tumor promotion on the basis of the two-stage DMBA-TPA carcinogenesis test in vivo. Soyasaponin I reduced the number of papillomas per mouse at about 40% even at 20 weeks [152]. 

DNA was capable of malignantly transforming NIH 3T3 cells in DNA transfection studies (411). Studies in our laboratory (41) indicate that initiation alone or repetitive TPA treatments are insufficient to turn on the expression of the Ha-raa oncogene in adult SENCAR mouse epidermis. Initiation followed by either one or six weeks of TPA treatment also failed to activate Ha- ga expression. Like Balmain, we observed elevated levels of Ha-ras RNA in a percentage of papillomas and carcinomas tested. We have also found that the expression of c-sis. and c-aU are increased in the majority of carcinomas examined (42). It remains to be determined whether oncogene activation plays a critical role in multistage skin carcinogenesis. 

Active as inhibitor on two stage carcinogenesis test of mouse skin tumors induced by nitric oxide donor (NOR 1) and TPA. [44]... 

Anti-tumor promoting activity on a two-stage carcinogenesis test on mouse skin using DMBA and croton oil. Increase the life span of transplanted DLA and EAO harboring mice and reduces the volume of transplanted solid tumors [101]... 

In a similar screening, Konoshima et al. [72] studied the inhibitory effects of twenty-four 29-nor-cucurbitacin glucosides isolated from the roots of Cayaponia tayuya and found that five of them, cayaponosides B, B3, D, D3b, and C2, exhibited significant inhibitory effects on EBV activation induced by the tumor promoter TPA. Moreover, two of the cucurbitacins shown to be active in vitro, cayaponosides B and C2, Fig. (14), inhibited mouse skin tumor promotion in a two-stage in vivo carcinogenesis test. 

And, many compounds which showed strong inhibitory effects on the induction of EBV-EA by TPA have been shown to act as inhibitors of tumor promotion on two-stage carcinogenesis test in vivo [15-21, 27-29]. The one of two-stage carcinogenesis test is on mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a... 

Fig. (3). Method of in vivo two-stage carcinogenesis test on mouse skin tumors.

The effects of 33 and 34 on a two-stage carcinogenesis test were investigated as well as 12 and 25. Both rotenoids 33 and 34, when applied continuously before each TPA treatment, significantly, delayed the formation of papillomas in mouse skin and reduced the rate of papilloma-bearing mice (about 80% and 60% reduction as compared with the positive control even at 20 weeks of promotion, respectively). Furthermore, these two compounds reduced the number of papillomas per mouse (about 90% and 70% reduction even at 20 weeks of promotion) as shown in Fig. (6). 

Further, 39 showed the remarkable inhibitory effects on in vivo two-stage carcinogenesis of mouse skin tumor. In the tested group treated with 39, only 40% of mice bore papillomas at 10 weeks of promotion and 60% of mice bore papillomas at 17 weeks of promotion, and about 2 papillomas were formed per mouse at 10 weeks of promotion and only about 6 papillomas were formed per mouse after 20 weeks of promotion. 

The inhibitory activity of 163 (and also 165) on EBV-EA activation at equivalent mol ratio/TPA was greater than that of other natural products previously tested described above. On the basis of these results, the inhibitory effects of 163 on two-stage carcinogenesis of mouse skin and pulmonary tumors were investigated [64]. 

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