Combination Effects in Chemical Carcinogenesis (Experimental Results)

Schmähl, D

doi:10.1159/000225109

Cited by 27 publications

(2 citation statements)

References 4 publications

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“…Chemical carcinogens can have additional synergic or antagonistic effects when simultaneously presented in different metabolic ways (Schmahl 1976, Lutz 2001. The synergy between smoking and exposure to asbestos favours lung cancer development as a consequence of chronic inflammation and compensatory cell proliferation.…”

Section: Absorption and Metabolism Of Chemical Carcinogensmentioning

confidence: 99%

Chemical carcinogenesis

Oliveira

Colaço

Chaves

et al. 2007

An. Acad. Bras. Ciênc.

140

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The use of chemical compounds benefits society in a number of ways. Pesticides, for instance, enable foodstuffs to be produced in sufficient quantities to satisfy the needs of millions of people, a condition that has led to an increase in levels of life expectancy. Yet, at times, these benefits are offset by certain disadvantages, notably the toxic side effects of the chemical compounds used. Exposure to these compounds can have varying effects, ranging from instant death to a gradual process of chemical carcinogenesis. There are three stages involved in chemical carcinogenesis. These are defined as initiation, promotion and progression. Each of these stages is characterised by morphological and biochemical modifications and result from genetic and/or epigenetic alterations. These genetic modifications include: mutations in genes that control cell proliferation, cell death and DNA repair -i.e. mutations in proto-oncogenes and tumour suppressing genes. The epigenetic factors, also considered as being non-genetic in character, can also contribute to carcinogenesis via epigenetic mechanisms which silence gene expression. The control of responses to carcinogenesis through the application of several chemical, biochemical and biological techniques facilitates the identification of those basic mechanisms involved in neoplasic development. Experimental assays with laboratory animals, epidemiological studies and quick tests enable the identification of carcinogenic compounds, the dissection of many aspects of carcinogenesis, and the establishment of effective strategies to prevent the cancer which results from exposure to chemicals.

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Section: Absorption and Metabolism Of Chemical Carcinogensmentioning

confidence: 99%

Chemical carcinogenesis

Oliveira

Colaço

Chaves

et al. 2007

An. Acad. Bras. Ciênc.

140

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“…However, during the last 5 to 10 years toxicologists from academia, research institutes, and industry, as well as regulators, gradually paid more and more attention to the development of research programs on toxicology and risk assessment of chemical mixtures, recognizing that simultaneous or sequential exposure to large numbers of chemicals is a reality of potential health concern (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34).…”

mentioning

confidence: 99%

Toxicology of chemical mixtures: international perspective.

Feron

Cassee

Groten

1998

Environ Health Perspect

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In the United States, research programs on the toxicology of chemical mixtures have existed for several decades. These programs vary from real-life case studies (e.g., on contaminated soil or lakes, recycled drinking water, dioxins, diesel exhaust, coal tars, and chemicals released from hazardous waste sites) to the development of methods for the safety evaluation and risk assessment of both simple and complex mixtures such as new approaches for identification of genotoxic components in complex mixtures and the weight-of-evidence (WOE) approach, using interaction data in component-based risk assessment of mixtures (1-5). Moreover, in the United States, programs on more basic issues in mixture toxicology include physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling of mixtures (6-8), the use of physicochemical concepts to mechanistic elucidation of toxicologic interactions (9), the development of statistical designs for experimental studies of mixtures (10-13),

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Potentiation of dimethylhydrazine bowel carcinogenesis in rats

Steele

Crissey

Gittes

et al. 1981

Cancer

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An animal model of organ-specific chemical carcinogenesis has been used to study environmental effects on the incidence of human colorectal adenocarcinoma. Wistar/Furth weanling rats underwent connection of their urinary and fecal streams (ureterosigmoidostomy), connection of their urinary and fecal streams with proximal fecal diversion (rectal bladder), or sham operations. Age-matched, unoperated control and operated animals then received either no carcinogen, 1,2-dimethylhydrazine (DMH) 20 mg/kg body weight, s.c. once weekly for 16 weeks, N-[4-(5-nitro-2-furyl)-2-thiazolylformamide (FANFT) 0.2% of the feed for 16 weeks, or DMH + FANFT concurrently. Thirty-three weeks after carcinogen exposure, surviving animals were killed and examined for bowel and urinary bladder tumors. The incidence of adenocarcinoma of the colon adjacent to the junction between bladder and bowel was significantly higher in animals after ureterosigmoidostomy compared with animals whose fecal stream had been proximally diverted (14/22 vs. 0/34, P less than 0.001). This effect was not dependent upon chemical carcinogen exposure. Nonexposed animals still developed a significantly higher incidence of colon adenocarcinomas adjacent to their bladder-bowel junctions as compared with animals with proximal fecal diversion (5/8 vs. 0/13, P less than 0.01). In unoperated or sham operated animals, adenocarcinomas of the bowel occurred in 33% of DMH-treated animals and transitional cell carcinomas of the urinary bladder in 33% of the FANFT-treated animals. After concurrent exposure to both carcinogens, no increased incidence of bladder tumors was noted when compared with FANFT treatment alone. However, the number of animals with one or more adenocarcinomas of the bowel (22/30 vs. 17/50, P less than 0.001), the mean number of tumors per animal (2.1 +/- 0.2 vs. 1.1 +/- 0.1, P less than 0.01), and the invasiveness of the tumors were all increased after DMH + FANFT as compared with DMH exposure alone. The carcinogenic potential of direct bladder to bowel connection with intact fecal and urinary streams, and the potentiation by FANFT of DMH-induced colon carcinogenesis may have implications in the genesis of human colorectal cancer.

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Combination Effects in Chemical Carcinogenesis (Experimental Results)

Cited by 27 publications

References 4 publications

Chemical carcinogenesis

Chemical carcinogenesis

Toxicology of chemical mixtures: international perspective.

Potentiation of dimethylhydrazine bowel carcinogenesis in rats

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