Environmental sources, carcinogenicity, mutagenicity, metabolism and DNA binding of nitrogen and sulfur heterocyclic aromatics

Warshawsky, David

doi:10.1080/10590509209373411

Cited by 75 publications

(59 citation statements)

References 185 publications

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“…(273). 7H-Dibenzo[c,g]carbazole was distributed to the liver, kidney, brain, and fat, and the highest concentrations were observed in the intestine; 6 h after administration, five times as much compound was observed in the feces as in the urine (271 (3,11). The IARC classifies 7H-dibenzo[c,g]carbazole as a 2B carcinogen (possible human carcinogen) based on sufficient evidence that 7H-dibenzo[c,g]carbazole is carcinogenic in experimental animals (7).…”

Section: Workplace Methodsmentioning

confidence: 98%

“…None of the 11H-benzo[a] carbazole was active. 7H-Benzo[c]carbazole was weakly active to skin, and 10-methyl derivative was somewhat more active subcutaneously (11). Based on the data, the IARC indicated that carbazole is a class 3 carcinogen because of limited evidence that carbazole is carcinogenic in animals (3).…”

Section: Carcinogenesismentioning

confidence: 97%

“…The activity of these compounds depends upon the functional groups attached to specific sites. For example, when the 7-position is substituted by a methyl group, the activity increases for benz[c]acridine and derivatives (11). Benz[a]acridine and benz [c]acridine are classified by the IARC as group-3 carcinogen-based limited animal data and no human data.…”

Section: Carcinogenesismentioning

confidence: 99%

“…Exposure to a variety of complex mixtures such as soot, coal tar and pitch, mineral oils, coal gasification residues, and cigarette smoke has historically been associated with cancer mortality (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). These mixtures contain homocyclic and heterocyclic polycyclic aromatic hydrocarbons, many of which are well-known experimental carcinogens.…”

Section: Introduction To Class Of Chemicalsmentioning

confidence: 99%

“…Aromatic hydrocarbons differ vastly in chemical, physical, and biological properties from the aliphatic and alicyclic hydrocarbons, with increased toxicity to humans and other mammals. Of prime importance in this respect is the carcinogenicity of these hydrocarbons (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11).…”

Section: Introduction To Class Of Chemicalsmentioning

confidence: 99%

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Polycyclic Aromatic Hydrocarbons and Azaaromatic Compounds

Baxter¹,

Warshawsky²

2012

Patty's Toxicology

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Polycyclic aromatic hydrocarbons (PAHs) are moderately reactive, but undergo photochemical degradation in the atmosphere, and are widely used as chemical raw materials. Aromatic hydrocarbons cause local irritation and changes in endothelial cell permeability and are absorbed rapidly. Accumulation of aromatic hydrocarbons in marine animals occurs to a greater extent and retention is longer compared to alkanes. Toxicity of polynuclear aromatics has been reported comprehensively. It has been reported that exposure to a variety of complex mixtures containing these chemicals, such as soot, coal tar and pitch, mineral oils, coal gasification residues, and cigarette smoke has historically been associated with induction of cancer. Naphthalene causes cataracts in the eyes of experimental animals. Its vapors may cause severe systemic injury. Alkylbenzenes are readily aspirated and produce instant death via cardiac arrest and respiratory paralysis. In general, the acute toxicity of alkylbenzenes is higher for toluene than that for benzene and decreases further with increasing chain length of the substituent, except for highly branched C 8 to C 18 derivatives. Polycyclic aromatic hydrocarbons are metabolized through epoxides and hydroxides and are excreted as conjugates.

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Section: Workplace Methodsmentioning

confidence: 98%

Section: Carcinogenesismentioning

confidence: 97%

Section: Carcinogenesismentioning

confidence: 99%

Section: Introduction To Class Of Chemicalsmentioning

confidence: 99%

Section: Introduction To Class Of Chemicalsmentioning

confidence: 99%

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Polycyclic Aromatic Hydrocarbons and Azaaromatic Compounds

Baxter¹,

Warshawsky²

2012

Patty's Toxicology

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Frequent Ha-ras mutations in murine skin and liver tumors induced by 7H-dibenzo[c,g]carbazole

Mitchell

Warshawsky

1999

Mol. Carcinog.

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7H-dibenzo[c,g]carbazole (DBC) is a potent liver and skin carcinogen when topically applied to the back skin of mice. This compound is found in complex mixtures produced during incomplete combustion of fossil fuels as well as in wood and tobacco smoke. The objective of this study was to elucidate the mechanism of action of this compound by assessing the Ha-ras mutational spectra of skin and liver tumors induced in a mouse model system. Low doses (50 nmol) and high doses (100 nmol) of DBC were applied topically to the backs of Hsd:ICR(Br) mice twice weekly. No treatment and solvent application were used as controls. After the mice were killed, the skin and liver tumors were removed, DNA was isolated, and tumor DNA was screened for Ha-ras codon 12, 13, and 61 mutations by using an enriched polymerase chain reaction method. Mutations were confirmed by reverse cyclic dideoxy sequencing. No mutations were found in codons 12 and 13 of DBC-induced tumors, whereas one acetone-control tumor had a codon 13 mutation. Sixty-seven percent of skin tumors and 45% of liver tumors induced by high doses of DBC and 67% of skin tumors induced by low doses of DBC contained codon 61 mutations, whereas liver tumors induced by low doses of DBC did not. The codon 61 mutations were exclusively A:T-->T:A transversions within the second base (CAA-->CTA). These results indicate that DBC is a unique polycyclic aromatic hydrocarbon in that it induces both skin and liver tumors upon topical application and that the mutational spectra are the same in tumors from two target organs, skin and liver, yet different from tumors from a third target organ, lung.

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