Potentiation of 2,6-dinitrotoluene genotoxicity in Fischer-344 rats by pretreatment with Aroclor 1254☆

Chadwick, Robert W.; George, S. Elizabeth; Kohan, Michael J.; Williams, Ron; Allison, J. C.; Hayes, Y. O.; Chang, Jer Jang

doi:10.1016/0300-483x(93)90178-u

Cited by 16 publications

(17 citation statements)

References 29 publications

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“…increased the production of DNT-derived urinary mutagens (Table 2), and potentiated the formation of DNT-derived DNA adducts in the liver (Figure 3 and Table 3). Like the previously studied Aroclor 1254 (Chadwick et al, 1993), creosote significantly increased the bioactivation of DNT to mutagenic metabolites after only 1 wk of treatment (Table 2) Liver of rat gavaged daily with 50 mg/kg creosote for 5 wk. (E) Liver of rat gavaged daily with 50 mg/kg coal tar creosote for 5 wk that receives a po injection of 75 mg/kg DNT.…”

Section: Discussionmentioning

confidence: 91%

“…Therefore, reduced nitroreductase activity in the small intestine would favor the transport of more unaltered DNT to the liver and its subsequent conversion to genotoxic metabolites. Previously it has been found that reduced nitroreductase in the small intestine preceded the elevated excretion of mutagenic DNT metabolites in the urine and enhanced formation of hepatic DNA adducts in animals pretreated with various environmental toxicants (Chadwick et al, , 1993George et al, 1991). Many variables can influence the extent of DNA adduct formation, such as competition between metabolic activation and detoxication, DNA repair, the extent of cell replication, and cell death.…”

Section: Discussionmentioning

confidence: 98%

“…In this study, the genotoxic effects of two of these environmental contaminants, 2,6-dinitrotoluene (DNT) and creosote, are investigated. Previous work in this laboratory indicated that pretreatment of rats with pentachlorophenol (PCP) George et al, 1991) or with Aroclor 1254 (Chadwick et al, 1993) potentiated the genotoxicity of the industrial chemical DNT. On the other hand, pretreatment with the organochlorine herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) produced only a transient antagonism of DNT toxicity (George et al, 1992).…”

Section: R W Chadwick Et Almentioning

confidence: 99%

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Potentiation of 2,6‐dinitrotoluene genotoxicity in fischer 344 rats by pretreatment with coal tar creosote

Chadwick

George

Kohan

et al. 1995

Journal of Toxicology and Environmental Health

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Pretreatment of male Fischer 344 rats for 5 wk with coal tar creosote, a coal distillation product that is widely used as a wood preservative, potentiated the excretion of urinary mutagens in 2,6-dinitrotoluene (DNT) treated rats. Creosote increased the bioactivation of DNT to significantly greater levels of urinary genotoxic metabolites and/or formed DNA adducts in the liver. A significant increase in the excretion of mutagenic DNT metabolites was observed after the first week of creosote treatment, peaked at wk 3, and then decreased by 33% after 5 wk of treatment. Nevertheless, there was a significant increase (66%) in the formation of DNT-derived DNA adducts in the livers of rats treated with DNT plus creosote at wk 5. Increased cecal beta-glucuronidase activity and reduced small intestinal nitroreductase activity may play roles in the bioactivation of DNT. The excretion of mutagenic DNT metabolites supplies useful information about the bioactivation of DNT; it does not provide a useful index of DNT-derived hepatic DNA adduct formation. Such interactions could be important to predictive risk assessment because the overall cancer risk of such chemical mixtures may exceed the sum of the component risks.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 98%

Section: R W Chadwick Et Almentioning

confidence: 99%

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Potentiation of 2,6‐dinitrotoluene genotoxicity in fischer 344 rats by pretreatment with coal tar creosote

Chadwick

George

Kohan

et al. 1995

Journal of Toxicology and Environmental Health

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“…A metabolite, 2-amino-6-nitrotoluene, gave the same adducts as 2,6-DNT, but at 30-fold lower levels (158). Intestinal microflora were important in activating 2,6-DNT to mutagenic metabolites (159), and the genotoxicity was increased by pretreating the rats with the enzyme inducers Aroclor 1254 or creosote (160,161 …”

Section: Toxic Effectsmentioning

confidence: 87%

Aromatic Nitro and Amino Compounds

Bingham¹,

McGowan²

2012

Patty's Toxicology

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Logically, aromatic nitro and amino compounds should be discussed together because their toxic responses are often similar due to a common metabolic intermediate. Synthetically, amines are generally derived from nitro compounds, but in some cases nitro compounds can be prepared through amines when other methods fail to afford specific compounds. There are good and bad attributes to these types of compounds. Some act as sensitizers and contingent on physical properties may be absorbed through the skin or mucous membranes. They may also cause methemoglobinemia, depending on such factors as the structure and the particular organism. Some members of this class are known as animal and human carcinogens; for humans, the urinary bladder is the most prominent target organ. Nevertheless, these compounds and their derivatives have enlivened our world through their use as dyestuff intermediates or as photographic chemicals, they alleviate pain as components of widely used analgesics, and they cushion or insulate us through their use in flexible and rigid foams. Other important uses include production of pesticides, including herbicides and fungicides, as ingredients in adhesives, paints and coatings, antioxidants, explosives, optical brighteners, rubber ingredients, and as intermediates in many other products.

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“…Repeated doses of Aroclor 1254 did not alter hepatic levels of DNA adducts (as measured by 32 P-postlabelling) in male Sprague-Dawley (given two intraperitoneal doses of 500 mg/kg bw) or male Fischer 344 rats (given 35 oral doses of 25 mg/kg bw) compared with controls (Nath et al, 1991;Chadwick et al, 1993).…”

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confidence: 99%

Polychlorinated biphenyls and polybrominated biphenyls

Walker¹

2001

Organic Pollutants

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Potentiation of 2,6-dinitrotoluene genotoxicity in Fischer-344 rats by pretreatment with Aroclor 1254☆

Cited by 16 publications

References 29 publications

Potentiation of 2,6‐dinitrotoluene genotoxicity in fischer 344 rats by pretreatment with coal tar creosote

Potentiation of 2,6‐dinitrotoluene genotoxicity in fischer 344 rats by pretreatment with coal tar creosote

Aromatic Nitro and Amino Compounds

Polychlorinated biphenyls and polybrominated biphenyls

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