SKH-1 mouse skin painting: A short-term assay to evaluate the tumorigenic activity of cigarette smoke condensate

Roemer, E.; Ottmueller, T.H.; Urban, H.-Jörg; Baillet-Mignard, C.

doi:10.1016/j.toxlet.2009.10.019

Cited by 7 publications

(5 citation statements)

References 54 publications

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“…The in vivo tumour promoter-like carcinogenic activity of TPM has been established in the mouse skin painting assay for various strains of mice. A dose-dependent increase in skin tumours was seen after treatment with TPM from various cigarettes after 15-54 weeks of exposure (25)(26)(27)(28)(29). In several in vitro transformation assays, TPM has been shown to exhibit complete (i.e.…”

Section: Cigarette Smoke-induced Morphological Transformation Of Bhasmentioning

confidence: 99%

Cigarette Smoke-induced Morphological Transformation of Bhas 42 Cells In Vitro

Weisensee

Poth²,

Roemer

et al. 2013

Alternatives to Laboratory Animals

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In vitro cell transformation assays detect transformed cells that have acquired the distinct characteristics of malignant cells and thus model one stage of in vivo carcinogenesis. These assays have been proposed as surrogate models for predicting the non-genotoxic carcinogenic potential of chemicals. The Bhas 42 cell transformation assay, a short-term assay that uses v-Ha-ras-transfected Balb/c 3T3 cells, can detect the tumour promoter-like activities of chemicals, but has not previously been used with cigarette smoke. The particulate phase of cigarette smoke (total particulate matter [TPM]) is known to induce tumours in vivo in the mouse skin painting assay. Therefore, we investigated the ability of this Bhas cell assay to form morphologically transformed foci in vitro when repeatedly challenged with TPM from a standard research cigarette. TPM induced a dose-dependent increase in Type III foci, and a significant increase (up to 20-fold) in focus formation at moderately toxic concentrations between 5 and 60μg TPM/ml, with a peak at 20μg/ml. Three batches of TPM were tested in three independent experiments. Precision (repeatability and reproducibility) was calculated by using 0, 5, 10, and 20μg TPM/ml. Repeatability and reproducibility, expressed as the relative standard deviation obtained from the normalised slopes of the dose–response curves, were 17.2% and 19.6%, respectively; the slopes were 0.7402 ± 0.1247, 0.9347 ± 0.1316, and 0.8772 ± 0.1767 (increase factor*ml/mg TPM; mean ± SD); and the goodness of fit (r2) of the mean slopes, each derived from n = 6 repeats, was 0.9449, 0.8198, and 0.8344, respectively. This in vitro assay with Bhas 42 cells, which are regarded as already initiated in the two-stage paradigm of carcinogenesis (initiation and promotion), is able to detect cell transformation induced by cigarette smoke in a dose-dependent manner with a high sensitivity and good precision. Because this assay is fast and yields reliable results, it may be useful in product assessment, as well as for further investigation of the non-geno-toxic carcinogenic activity of tobacco smoke-related test substances.

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Section: Cigarette Smoke-induced Morphological Transformation Of Bhasmentioning

confidence: 99%

Cigarette Smoke-induced Morphological Transformation of Bhas 42 Cells In Vitro

Weisensee

Poth²,

Roemer

et al. 2013

Alternatives to Laboratory Animals

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“…for large-scale production used in mouse dermal tumorigenicity studies or for the analysis of low-yield chemicals). 68,69…”

Section: Hnb Aerosol Generation Systems and Methodologiesmentioning

confidence: 99%

“…for largescale production used in mouse dermal tumorigenicity studies or for the analysis of low-yield chemicals). 68,69 In the following sections, we describe the SM 2000 rotary smoking machine in its original (for cigarettes) and modified (for THS 2.2) versions. These smoking machines are routinely used for studies comparing THS 2.2 with cigarettes, including in vitro whole aerosol exposure studies and in vivo inhalation studies.…”

Section: Hnb Aerosol Generation With Rotary Smoking Machinesmentioning

confidence: 99%

State-of-the-art methods and devices for the generation, exposure, and collection of aerosols from heat-not-burn tobacco products

Boué

Goedertier

Hoeng

et al. 2020

Toxicology Research and Application

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Tobacco harm reduction is increasingly recognized as a promising approach to accelerate the decline in smoking prevalence and smoking-related population harm. Potential modified risk tobacco products (MRTPs) must undergo a rigorous premarket toxicological risk assessment. The ability to reproducibly generate, collect, and use aerosols is critical for the characterization, and preclinical assessment of aerosol-based candidate MRTPs (cMRTPs), such as noncombusted cigarettes, also referred to as heated tobacco products, tobacco heating products, or heat-not-burn (HNB) tobacco products. HNB tobacco products generate a nicotine-containing aerosol by heating tobacco instead of burning it. The aerosols generated by HNB products are qualitatively and quantitatively highly different from cigarette smoke (CS). This constitutes technical and experimental challenges comparing the toxicity of HNB aerosols with CS. The methods and experimental setups that have been developed for the study of CS cannot be directly transposed to the study of HNB aerosols. Significant research efforts are dedicated to the development, characterization, and validation of experimental setups and methods suitable for HNB aerosols. They are described in this review, with a particular focus on the Tobacco Heating System version 2.2. This is intended to support further studies, the objective evaluation and verification of existing evidence, and the development of scientifically substantiated HNB MRTPs.

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“…The use of the SEN-CAR mouse strain is well established, which is more sensitive than the B6C3F1 or Swiss CD-1 strains. Recently, the usefulness of the hairless (but not "nude") SKH-1 strain was demonstrated for the testing of cigarette smoke condensate (222). The skin painting assay employs a two-stage approach.…”

Section: Toxicity Testing In Vitro and In Vivomentioning

confidence: 99%

Influence of Additives on Cigarette Related Health Risks

Klus¹,

Scherer²,

Müller

2012

Beiträge Zur Tabakforschung International/Contributions to Tobacco Research

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Tobacco additives play an important role in the manufacturing and for the quality of tobacco products, particularly cigarettes and roll-your-own tobaccos. Attention is increasingly given to the potential effects of additives on consumer behavior and health. This review is intended to compile, collate and - to some degree - evaluate the wealth of pertinent scientific information available from the published literature and other special sources. At first, the reasons are set forth for the use of additives in cigarette manufacturing. In response to the growing controversy over the attractiveness and addictiveness of smoking, the clarification of terms and concepts is followed by a detailed discussion of two kinds of substances with particular relevance: Additives like ammonium compounds that are claimed to increase nicotine availability, and additives that are claimed to increase nicotine addictiveness.The composition and toxicity of mainstream smoke of cigarettes with and without additives are assessed in several respects. The potentials of pyrolysis studies are explored by looking at a number of key studies and some basic considerations regarding in vitro and in vivo toxicity testing are addressed. Five major literature reviews on additives published between 1994 and 2004, and the results of several comprehensive experimental studies covering a large range of additives, released between 2002 and 2012, are dealt with in detail. Single tobacco additives of particular importance (menthol, glycerol, 1,2-propylene glycol, sorbitol, sugars, cocoa, licorice, citric acid, triacetin, and ammonium compounds) are discussed in dedicated chapters, which are generally subdivided into special sections: Use and toxicological assessment; inclusion level in cigarettes, transfer and pyrolysis; attractiveness and addictiveness; effect on cigarette mainstream smoke composition; effect on cigarette mainstream smoke toxicity. Epidemiological findings and data obtained by the biomonitoring of smokers consuming cigarettes with and without additives are compiled and interpreted specifically for American blend cigarettes, Virginia cigarettes, “French” (dark) cigarettes and menthol cigarettes whereby the focus is on the effects of additives on smoking topography and potential health risks.Opinionated reviews were published in recent years that are compromised by arbitrary selection of sources and unbalanced views. Leaving those unconsidered, the aggregated scientific knowledge shows that tobacco additives have only occasional and limited effects on cigarette mainstream smoke composition, which are almost never reflected in the results of toxicological in vitro assays or in vivo studies. This supports the conclusion that tobacco additives are not likely to increase the known health risks of smoking. There is also no evidence for sustaining claims that certain additives increase nicotine availability or nicotine addictiveness.

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SKH-1 mouse skin painting: A short-term assay to evaluate the tumorigenic activity of cigarette smoke condensate

Cited by 7 publications

References 54 publications

Cigarette Smoke-induced Morphological Transformation of Bhas 42 Cells In Vitro

Cigarette Smoke-induced Morphological Transformation of Bhas 42 Cells In Vitro

State-of-the-art methods and devices for the generation, exposure, and collection of aerosols from heat-not-burn tobacco products

Influence of Additives on Cigarette Related Health Risks

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