Comparison of Complete Carcinogenesis and Tumor Initiation and Promotion in Mouse Skin: The Induction of Papillomas by Tumor Initiation-Promotion a Reliable Short Term Assay

Abstract

Downloaded from 84 SLACA ET AL.There is a good correlation between the tumor-initiating activities of PAH and their abilities to bind covalently to DNA. In addition, various inhibitors of PAH tumor initiation show a strong correlation with their abilities to inhibit the binding of the PAH to DNA and their anti-tumor initiating activities. There is also a good correlation between the promoting abilities of phorbol esters to promote tumors and their abilities to induce ornithine decarboxylase (ODC), cell proliferation and dark basal keratinocytes. When other nonpromoting hyperplastic agents are used, only dark cell induction correlates with promotion. Certain polyamines and prostaglandins can enhance phorbol ester tumor promotion. Anti-inflammatory steroids, retinoids, and protease inhibitors are potent inhibitors of tumor promotion. They inhibit tumor promotion by inhibiting either the 7 2-0-tetradecanoylphorbol-13 -acetate (TPA) induced cell proliferation, ODC and/or dark basal keratinocytes. Certain weak promoters such as mezerein which mimics TPA in many biochemical and morphological effects are potent second step promoters in a two-stage promotion regimen.6 . Co-initiating and Co-promoting Agents 7. Anti-carcinogenesis 8.

SENCAR mouse skin tumorigenesis model versus other strains and stocks of mice.

“…A number of environmentally important complex mixtures have also been extensively studied for skin-carcinogenic and/or tumor-initiating activity in the SEN-CAR mouse (28)(29)(30)(31)(32). Of the complex mixtures tested, coke oven main and roofing tar both had strong skin carcinogenic and tumor-initiating activity, whereas the Nissan diesel exhaust sample was only a strong tumor initiator.…”

Chemical characterization and toxicologic evaluation of airborne mixtures. Tumorigenicity studies of Diesel Fuel-2, Red Smoke Dye and Violet Smoke Dyes in the SENCAR Mouse Skin Tumorigenesis Bioassay System

“…These results indicate that the mouse skin tumorigenesis bioassay seems particularly well suited for evaluation of the tumorigenic potential of compounds and "mixtures known to be dermal carcinogens and also some compounds and mixtures that are thought to cause cancers at other sites (Nesnow et al, 1982).…”

Comparison of the tumorigenic response of SENCAR and C57BL/6 mice to benzo(a)pyrene and the inter-experimental variability over a three-year period.

“…The mean responses (+ SD) and ranges for papilloma incidence for male and female mice were 87 + 10% (65% to 100%) and 86 ± 10% (65 to 100%), respectively (Figs. 3 and 4). The coefficient of variation was the same for both sexes at 12%.…”

“…Because of its demonstrated increased sensitivity to the tumor-initiating effects of DMBA and benzo(a)pyrene [B(a)P] (3,4), this mouse has been the subject of intensive investigations using both complex mixtures and pure chemicals. We have reported in a series of publications the tumorinitiating, tumor-promoting, tumor-coinitiating, and complete carcinogenic properties of a wide variety of complex mixtures, including gasoline exhausts, diesel exhausts, coke oven and roofing tar emissions, and cigarette smoke condensate (5)(6)(7)(8).…”