Carcinogenicity and Chronic Toxicity of 1,4-Dichloro-2-nitrobenzene in Rats and Mice by Two Years Feeding

Yamazaki, Kazunori; Aiso, Shigetoshi; Matsumoto, Michiharu; Kano, Hirokazu; Arito, Heihachiro; Nagano, Kasuke; Yamamoto, Seigo; Matsushima, Taijiro

doi:10.2486/indhealth.44.230

Cited by 8 publications

(4 citation statements)

References 23 publications

(29 reference statements)

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“…Chlorinated benzenes (CBs) and their metabolites have been the focus of biochemical and toxicological studies since CBs are commonly used in industrial processes [1][2][3][4][5][6]. Chlorobenzene is known for targeting reproductive tissues and the nervous system [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…Chlorobenzene is known for targeting reproductive tissues and the nervous system [3,4]. p-Dichlorobenzene, a component for pesticides and mothballs, was found to be associated with neurotoxic effects and carcinogenicity [5,6]. The degradation pathways of CBs were found to be similar to that of polycyclic aromatic hydrocarbons (PAHs) leading to the formation of quinone metabolites [7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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Biological implications of 2-chlorocyclohexa-2,5-diene-1,4-dione toward ribonuclease A

Vaughn¹,

Redman²,

Kang³

et al. 2013

ABB

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2-Chlorocyclohexa-2,5-diene-1,4-dione (CBQ) or 2-chloro1,4-benzquinone is one of the common metabolites of polycyclic aromatic hydrocarbons generated through industrial processes. This report describes the biological effects of CBQ toward ribonuclease A (RNase). We also investigated the inhibition of RNase modifications and the reactivity of CBQ toward selected amino acids. The study was carried out by incubating RNase or amino acids with CBQ in a concentration-and a time-dependent manner at 37˚C and pH 7.0. SDS-PAGE results showed oligomerization as well as polymeric aggregation of RNase when incubated with CBQ as early as in 10 min. CBQ-induced RNase modifications were inhibited in the presence of NADH or ascorbic acid. CBQ reactivity toward selected amino acids was also evaluated by determining the second-order rate constants for the reactions of CBQ with selected amino acids. It was found that the reactivity toward CBQ decreased in the order of lysine > threonine > serine >> aspartate > cysteine.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biological implications of 2-chlorocyclohexa-2,5-diene-1,4-dione toward ribonuclease A

Vaughn¹,

Redman²,

Kang³

et al. 2013

ABB

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show abstract

“…Toxic effects of aromatic compounds containing chlorine and nitro groups have recently attracted a great deal of attention Matsumoto et al, 2006aMatsumoto et al, , 2006bYamazaki et al, 2006). Kano et al (2006) reported that 2,4-dichloro-1-nitrobenzene (2,4-DCNB) in the diet induced kidney tumors in rats.…”

Section: Introductionmentioning

confidence: 99%

Identification of an N-acetylcysteine conjugate in the urine after oral administration of 2,4-dichloro-1-nitrobenzene to rats

et al. 2009

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“…Third, the renal cell carcinoma found in the present study had a histopathologically pleomorphic appearance. Fourth, since o-CNB was reported to be a potent mutagen with S9 activation (JETOC, 1997), possible mutagenic metabolites of o-CNB, which were presumably biotransformed from a cysteine conjugate of o-CNB metabolite, N-acetyl-S-(2-nitrophenyl)-L-cysteine (Bray et al, 1956), by β-lyase in the kidney, might act directly on the renal DNA, as suggested by Yamazaki et al (2006) who demonstrated positive nephrocarcinogenicity in male F344 rats fed 1,4-dichloro-2-nitrobenzene, a structurally similar chemical of o-CNB, for 2 years. Therefore, it can be suggested that renal cell tumors are causally related to the long-term administration of o-CNB rather than to CPN.…”

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confidence: 99%

Two-Year Feed Study of Carcinogenicity and Chronic Toxicity of Ortho-Chloronitrobenzene in Rats and Mice

Matsumoto

Umeda

Senoh³

et al. 2006

J. Toxicol. Sci.

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-Carcinogenicity and chronic toxicity of ortho-chloronitrobenzene (o-CNB) were examined by feeding groups of 50 F344 rats and 50 BDF 1 mice of both sexes o-CNB-containing diets for 2 years. The dietary concentration of o-CNB was 0, 80, 400 or 2000 ppm (w/w) for rats and 0, 100, 500 or 2500 ppm for mice. The 2-year administration of o-CNB produced a dose-dependent increase in incidences of hepatocellular adenomas and carcinomas in rats and mice of both sexes and hepatoblastomas in mice of both sexes. Incidences of altered cell foci in the liver were increased in the o-CNB-fed rats of both sexes. Metastasis from mouse malignant liver tumors occurred predominantly in the lung. The hepatocarcinogenic response to o-CNB was found to be more potent in mice than in rats. Marginally increased incidences of renal cell adenomas in the 2000 ppm-fed female rats and renal cell carcinomas in the 2000 ppm-fed male rats were noted, together with a significantly increased incidence of atypical tubule hyperplasias. Spontaneous, age-related chronic progressive nephropathy was exacerbated in a dose-related manner, and caused the death of 47 male rats fed 2000 ppm before the end of the 2-year administration period. The highest dose levels of o-CNB except for the administration of 2000 ppm to male rats were thought to meet the criteria of the maximum tolerated dose set by both NCI and IARC guidelines. Causative factors of o-CNB-induced carcinogenicity were discussed with reference to our previous rodent studies of subchronic toxicity of o-CNB and carcinogenicity and chronic toxicity of para-chloronitrobenzene.

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Carcinogenicity and Chronic Toxicity of 1,4-Dichloro-2-nitrobenzene in Rats and Mice by Two Years Feeding

Cited by 8 publications

References 23 publications

Biological implications of 2-chlorocyclohexa-2,5-diene-1,4-dione toward ribonuclease A

Biological implications of 2-chlorocyclohexa-2,5-diene-1,4-dione toward ribonuclease A

Identification of an N-acetylcysteine conjugate in the urine after oral administration of 2,4-dichloro-1-nitrobenzene to rats

Two-Year Feed Study of Carcinogenicity and Chronic Toxicity of Ortho-Chloronitrobenzene in Rats and Mice

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