Tumorigenic potency

Clive D. 1977. A linear relationship between tumorigenic potency in vivo and mutagenic potency at the heterozygous thymidine kinase (TK+/-) locus of L5178Y mouse lymphoma cell coupled with mammalian metabolism. Dev Toxicol Environ Sci 2 241-247. 

Bailer, A. John, and Christopher J. Portier. 1993. An Index of Tumorigenic Potency. Biometrics 49 357-65. 

The assay system described in the present study should be useful in screening potential metal carcinogens for their ability to induce transformation. However, further work is required to demonstrate and validate that each of the various metals induce neoplastic transformation in tissue culture. A statistically significant number of transformed colonies induced by exposure of cells to each of the metal compounds must be cloned and derived into cell lines. The tumorigenic potency of these various cell lines must be tested in nude mice. 

Subsequent to the publication of the Preussmann and Stewart review (2991), Deutsch-Wenzel et al. (956a) reported that in a skin-painting study with N -nitrosonornicotine (NNN), tumors were initiated at the site of application. The specific tumorigenic potency of NNN was estimated to be only 0.8% of that of B[a]P. However, no dose response relationship was observed with NNN over a treatment range of 12.5 to 200 pg. 

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. 

Studies on experimental animals have indicated its tumorigenic potency. Repeated inhalation of dimethyl snlfate vapors cansed tumors of nasal cavity and thorax in rats. Repeated subcutaneous injections of the liq-nid produced local sarcomas. In hnmans, however, its carcinogenicity has not been established. The U.S. National Toxicology Program has classified this componnd as Reasonably anticipated to be carcinogenic to human (NTP 1998). 

Chrysotile and croci-dolite asbestos, erion-ite, man made fibres Rat pleural meso-thelial cells Cytotoxicity assessed by the 3-(4,5-dimethyl-tniazol-2-yl)-2,5-diphenyltetrazolium bromide assay The tumorigenic potency of fibres may be related to the fibre dimensions, to their surface properties on in vivo biopersistence. Renier et al. (1992)... 

Fig. 11.6 Histogram of 343 substances analyzed for their tumorigenic potency over lifetime exposure showing a normal distribution. From this analysis it was assumed that a probability can be calculated for most compounds to cause cancer. From Rulis (1987). Credit Republished with permission of Taylor and Francis Group LLC Books, from Chap. 2 De Minimis and the Threshold of Regulation, Fig. 1 Histogram and nonlinear least squares best fit Gaussian to the potencies of Gold et al., authored by Rulis (1987), ISBN 978-087371-047-3. Copyright 1987 permission conveyed through the Copyright Clearance Center, Inc...

In order to express the carcinogenic response or potency, a dose descriptor is used, for example the Tumorigenic Dose (TD). The TD is often set at a defined incidence, for example 5%, the TD5, defined as the dose (or concentration) associated with a 5% incidence of mmors. The dose descriptor can serve as the basis for development of an Exposure/Potency Index (EPl), which is the estimated daily human exposure divided by the TD. A calculated EPl of 10 for the TD5 represents a one million-fold difference between the human exposure and that at the lower end of the dose-response curve, on which the estimate of potency is based. 

The 16(17)-ene compounds 10 and 13 were protonated at the D-ring double-bond to form stable a-Phe-substituted carbocations. Although the ease of formation and stability of both carbocations lOH" " and 13H+ implicated their potency, compound 13 is a stronger tumorigen than 10, which led to the suggestion of an additive effect. 

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