Polycyclic aromatic hydrocarbons in human bronchial carcinoma

Tomingas, R.; Pott, F.; Dehnen, Walter

doi:10.1016/s0304-3835(75)96635-5

Cited by 16 publications

(6 citation statements)

References 4 publications

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“…As environmental pollution progresses, the amount of chemical carcinogen chronically inhaled by the exposed human population will also increase. In particular, PAHs (such as methylcholanthrene) are globally distributed environmental pollutants known for their carcinogenic and mutagenic effects on humans (42)(43)(44)(45). Fibroblasts are also present in human tissues exposed to carcinogen as, for example, asbestosis, making it important to study if encapsulation of carcinogen can be found in humans, especially in the light of the report from the International Agency for Research on Cancer (Lyon, France) that diesel engine exhaust is definitely carcinogenic to humans (a group 1 carcinogen, which is actually the same category as methylcholanthrene; refs.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast-Specific Protein 1/S100A4–Positive Cells Prevent Carcinoma through Collagen Production and Encapsulation of Carcinogens

Zhang¹,

Chen

Liu

et al. 2013

Cancer Research

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Stromal restraints to cancer are critical determinants of disease but they remain incompletely understood. Here, we report a novel mechanism for host surveillance against cancer contributed by fibroblast-specific protein 1 (FSP1) þ / S100A4 þ fibroblasts. Mechanistic studies of fibrosarcoma formation caused by subcutaneous injection of the carcinogen methylcholanthrene (MCA) had suggested that IFN-g receptor signaling may restrict MCA diffusion by inducing expression of collagen (foreign body reaction). We tested the hypothesis that this reaction encapsulated MCA and limited carcinogenesis by determining whether its ability to induce fibrosarcomas was impaired in the absence of proliferating fibroblasts. We found that FSP1 þ /S100A4 þ fibroblasts accumulated around the carcinogen where they produced collagens, encapsulating MCA and protecting epithelial cells from DNA damage. Ablation of these cells at the site of MCA injection by local administration of ganciclovir in FSP-TK transgenic mice altered tumor morphology to an epithelial phenotype, indicating that, in the absence of encapsulating fibroblasts, MCA targeted epithelial cells. Notably, we showed that destruction of the fibrous capsule around the MCA by local injection of collagenase induced rapid tumor development in mice that were otherwise durably tumor free. Our findings demonstrate that the FSP1 þ /S100A4 þ fibroblasts prevent epithelial malignancy and that collagen encapsulation of carcinogens protects against tumor development. Together, this study provides a novel mechanism for host surveillance against cancer. Cancer Res; 73(9); 2770-81. Ó2013 AACR.

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Section: Discussionmentioning

confidence: 99%

Fibroblast-Specific Protein 1/S100A4–Positive Cells Prevent Carcinoma through Collagen Production and Encapsulation of Carcinogens

Zhang¹,

Chen

Liu

et al. 2013

Cancer Research

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“…It is interesting to note that MCA-induced fibrosarcomas down-regulate expression of extracellular matrix proteins (36,38,39). PAHs are ubiquitous environmental pollutants, they are very stable (40) and can accumulate in the lung (41)(42)(43)(44). Since human exposure to benzo(a)pyrene has been estimated at 17 ng average daily intake from the air (45), one function of the foreign body reaction could be to protect from (frequent) tissue damage and concomitantly from (rare) malignant transformation by carcinogens.…”

Section: Discussionmentioning

confidence: 99%

“…Our results indicate that scars can be protective as the end product of MCA-encapsulation. Whether scar cancer results from inefficient encapsulation of carcinogen is not yet known, however, benzo(a)pyrene was detected in substantial amounts in lung tissues of smokers (41,44) and former smokers retain a substantial risk of developing lung cancer (50).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Methylcholanthrene-induced Carcinogenesis by an Interferon γ Receptor–dependent Foreign Body Reaction

Qin

Kim

Hemme

et al. 2002

The Journal of Experimental Medicine

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The foreign body reaction is one of the oldest host defense mechanisms against tissue damage which involves inflammation, scarring, and encapsulation. The chemical carcinogen methylcholanthrene (MCA) induces fibrosarcoma and tissue damage in parallel at the injection site. Tumor development induced by MCA but not due to p53-deficiency is increased in interferon-γ receptor (IFN-γR)–deficient mice. In the absence of IFN-γR, MCA diffusion and DNA damage of surrounding cells is increased. Locally produced IFN-γ induces the formation of a fibrotic capsule. Encapsulated MCA can persist virtually life-long in mice without inducing tumors. Together, the foreign body reaction against MCA prevents malignant transformation, probably by reducing DNA damage. This mechanism is more efficient in the presence of IFN-γR. Our results indicates that inflammation and scarring, both suspected to contribute to malignancy, prevent cancer in certain situations.

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“…Adequate methods are available to separate and quantify PAHs in biological materials such as adipose tissue (Gay et al 1980;Liao et al 1988;Modica et al 1982), lungs (Brandys et al 1989;Mitchell 1979;Tomingas et al 1976;Weston and Bowman 1991;Weyand and Bevan 1987a), liver Obana et al 1981;Rice et al 1985b), skin (Phillips et al 1987;Shugart et al 1983), hair (Alexandrov et al 1990), blood (Brandys et al 1989;Harris et al 1985;Haugen et al 1986;Phillips et al 1988;Shamsuddin et al 1985;Shugart 1986), urine (Au&up andSeremet 1986;Becher and Bjorseth 1985;Rogan et al 1990;Tolos et al 1990;Uziel et al 1987), and feces (Hecht et al 1979; to detect the presence of carcinogenic PAH adducts bound covalently to macromolecules (e.g., DNA).…”

Section: Identification Of Data Needsmentioning

confidence: 99%