Mouse skin tumor initiation-promotion and complete carcinogenesis bioassays: mechanisms and biological activities of emission samples.

Abstract

Extracts of soots obtained from various sources were applied to the skin of mice in an effort to identify carcinogens in these mixtures and to link these materials to the etiology of human cancer. Samples of coal chimney soot, coke oven materials, industrial carbon black, oil shale soot, and gasoline vehicle exhaust materials have been examined by this method. The studies reported here have been constructed to compare the carcinogenic and tumorigenic potency of extracts from various particulate emissions: coke ovens, diesel and gasoline vehicles and a roofing tar pot. Automobile emission samples were obtained by collecting the diluted and cooled exhaust on Teflon-coated glass fiber filters. Coke oven and roofing tar samples were particulate emission samples collected by impaction and filtration. The organic components associated with each of the particles were extracted with dichloromethane and dermally applied to SENCAR mice. All agents were applied as tumor initiators by using a five-dose protocol. Selected extracts were also applied as complete carcinogens and as tumor promotors. Statistical analyses of the resulting tumor data were performed by using nonlinear Poisson and probit models. The results from these experiments provide a suitable data base for comparative potency estimation of complex mixtures.

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.…”

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.

“…It is evident from these studies that statistical comparisons using normal or Poisson assumptions cannot be applied to these data. In this regard, we have reported on the use of a log probit analysis with nonzero background (16), which can be used to analyze mouse skin papilloma data (5,6). These data provide a useful tool for future comparisons of mouse skin tumor initiation data in SENCAR or other strains or stocks of mice with B(a)P or with other chemicals and can serve as a reference source for this information.…”

“…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). In terms of pure chemicals, many polycyclic aromatic hydrocarbons and their derivatives have been examined using the SENCAR mouse bioassay system (2-11).…”

Consensus report: mutagenicity and carcinogenicity of car exhausts and coal combustion emissions

“…In addition, the system is most responsive when the test material can be applied in a soluble form. The usefulness of the mouse skin system for studying airborne emissions has been reviewed (117).…”

“…Extensive studies have been conducted with SENCAR mice to assess the tumorigenic and carcinogenic activities of organic extracts from a variety of particulate emission sources: diesel and gasoline vehicles, coke oven and roofing tar (117,118). The SENCAR mouse strain was developed by genetically selecting for sensitivity in the 7,12-dimethylbenz(a)anthracene/12-0-tetradecanoyl-phorbol-13-acetate two-stage carcinogenesis model.…”