Squamous Carcinoma of the Forestomach and other Lesions in Mice following Oral Administration of 3:4:5:6-Dibenzcarbazole

Armstrong, Elizabeth C.; Bonser, Georgiana M.

doi:10.1038/bjc.1950.20

Cited by 21 publications

(2 citation statements)

References 6 publications

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“…A member of this chemical class, 7H-dibenzo[c,g]carbazole (DBC) is found in tobacco smoke, carbon black, emissions from exhaust stacks and automobiles and thus presents a potential environmental hazard and human health concern (8,14,24,40). Unlike many carcinogenic polycyclic aromatic hydrocarbons that are active only at the site of application, DBC has both local and systemic effects in the mouse when applied topically or by subcutaneous injection (3,18,39); it is a potent skin and liver carcinogen following topical application and also a lung carcinogen following intraperitoneal or intravenous administration (2,19,32,34). DBC was tested and studied for its potent hepatotropic and hepatocarcinogenic activities in XVII nc/z and C57BL6 mice, two strains with very low levels of spontaneous liver and lung tumors (37).…”

Section: Introductionmentioning

confidence: 99%

Induction of DNA Synthesis in Mouse Liver Following Increases of DNA Adduct Levels Elicited by Very Low Cumulative Doses of the Genotoxic Hepatocarcinogen 7H-dibenzo[c,g]carbazole

et al. 2001

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The purpose of this work was to investigate the administration of very low but repeated doses of a genotoxic carcinogen and an eventual correlation with cellular DNA synthesis. The compound 7H-dibenzo[c,g]carbazole is a genotoxic carcinogen in the mouse liver and was administered topically at the dose of 13.35 microg per animal every 2 days to give a total of 13 applications. Animals were sacrificed 48 hours after every 2 applications until the 10th treatment, then 48 hours after every treatment. Postulated genotoxic effects such as DNA adduct formation were detected by the 32P-post labeling assay. Liver sections were examined for microscopic changes and DNA synthesis. Results showed an increase of the total DNA adduct level in the liver throughout the study with a slowing down in the level after the sixth application of the compound. This change could correspond to the onset of DNA synthesis and to the moderate hepatocellular apoptosis which was observed. The DNA synthesis, which was considered to be secondary to the cytotoxicity induced by the high level of DNA adducts altering normal cellular activity, could also be the opportunity to fix the DNA adducts into heritable mutations. These results raise the question regarding the risk assessment in humans exposed regularly to very low doses of chemicals in the environment: for non-proliferating tissue, the regular accumulation of DNA adducts could remain silent until a "threshold level" is reached from which stimulation of the DNA synthesis may fix the DNA adducts into heritable mutations, eventually leading to tumors.

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Section: Introductionmentioning

confidence: 99%

Induction of DNA Synthesis in Mouse Liver Following Increases of DNA Adduct Levels Elicited by Very Low Cumulative Doses of the Genotoxic Hepatocarcinogen 7H-dibenzo[c,g]carbazole

et al. 2001

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“…More recently, DNA adducts in skin, lung and lymphocytes were found in rats after skin painting with undiluted bitumen fume condensates (Genevois et al, 1996). PAHs [for example, benzo [a]pyrene (B[a]P) or 3-methylcholanthrene] generally administered to animals by the oral or intraperitoneal routes were shown to have toxic effects on reproductive function (MacKenzie and Angevine, 1981), the cardiovascular system (Penn et al, 1981;Paigen et al, 1985), the bone marrow (Legraverend et al, 1983), the immune system (Hardin et al, 1992) and the liver (Armstrong and Bonser, 1950); for a review see IARC (1983).…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a New Bitumen Fume Generation System which Generates Polycyclic Aromatic Hydrocarbon Concentrations Proportional to Fume Concentrations

Binet

Bonnet²,

Brandt³

et al. 2002

The Annals of Occupational Hygiene

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Bitumen fumes emitted during road paving and roofing contain polycyclic aromatic compounds (PACs) of potential health concern. Little information is available for an experimental device devoted to inhalation experiments with animals exposed to bitumen fumes, and in all studies the systems were never validated for a range of fume concentrations, which prohibited their use for toxicological concentration-effect studies. Therefore, the purpose of this study was to validate a new experimental device able to generate bitumen fumes at different total particulate matter (TPM) concentrations with a linear correlation between TPM and the concentrations of different PACs, thus allowing toxicological dose-response studies with fumes representative of those in the field. Atmosphere samples collected from an animal exposure chamber allowed the determination of TPM, toluene soluble matter, polycyclic aromatic hydrocarbons (PAHs) and semi-volatiles. The particulate size distributions were determined in order to assess the deposition pattern in the respiratory tract. The temperature of 170 degrees C was chosen by analogy with the upper range of the temperature used during paving operations. The temperature of the air passing over the fume emission area was regulated to 20 degrees C and stirring of the heated bitumen was restricted to 90 r.p.m. The data show that the objective of developing a static fume generation system that reproducibly produces fumes in the inhalation chamber for specified target concentrations (TPM) were successful. The within-day variation coefficients for TPM were between 2.5 and 6.1%. The day-to-day variations for TPM concentration were between 4.1 and 5.8%. The concentrations of the 4-5 ring PAHs and the polycyclic aromatic sulphur heterocycles were proportional to the TPM concentration. The 2 and 3 ring PAH concentrations showed a deviation from proportionality with the TPM, probably due to their re-evaporation during sampling. The mass median aerodynamic diameter of airborne particles varied from 1.4 micro m at a fume concentration of 5 mg/m(3) to 3.2 micro m at 100 mg/m(3). In conclusion, this equipment was suitable for nose-only inhalation studies in the 5-100 mg/m(3) range of TPM. Bitumen fumes were generated with a good reproducibility under well-controlled conditions. Finally, the PAH profiles from atmospheric samples were in good agreement with those measured during road paving.

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Tissue-specific activities of methylated dibenzo[c,g]carbazoles in mice: Carcinogenicity, DNA adduct formation, and CYP1A induction in liver and skin

Taras-Valéro

Périn‐Roussel

Plessis

et al. 2000

Environ. Mol. Mutagen.

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Squamous Carcinoma of the Forestomach and other Lesions in Mice following Oral Administration of 3:4:5:6-Dibenzcarbazole

Cited by 21 publications

References 6 publications

Induction of DNA Synthesis in Mouse Liver Following Increases of DNA Adduct Levels Elicited by Very Low Cumulative Doses of the Genotoxic Hepatocarcinogen 7H-dibenzo[c,g]carbazole

Induction of DNA Synthesis in Mouse Liver Following Increases of DNA Adduct Levels Elicited by Very Low Cumulative Doses of the Genotoxic Hepatocarcinogen 7H-dibenzo[c,g]carbazole

Development and Validation of a New Bitumen Fume Generation System which Generates Polycyclic Aromatic Hydrocarbon Concentrations Proportional to Fume Concentrations

Tissue-specific activities of methylated dibenzo[c,g]carbazoles in mice: Carcinogenicity, DNA adduct formation, and CYP1A induction in liver and skin

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