Cumulative effects of chromosome aberrations and sister chromatid exchanges in rat liver induced <i>in vivo</i> by heterocyclic amines

Shibata, Shigeki; Daimon, Hirohiko; Asakura, Shô; Kawaguchi, Takashi; Yamatsu, Kiyomi; Furihata, Chie; Matsushima, Taijiro

doi:10.1093/carcin/15.2.285

Cited by 13 publications

(10 citation statements)

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“…This may be due to the fact that there is a high level of background endogenous DNA alteration in normal cells (about 1 in 10 8 ) (Randerath et al, 1993) and thus minor chemical-induced increments are not of biological significance (Nestmann et al, 1996). It would be interesting to determine whether such exposures lead to other genetic effects in the liver as has been reported for heterocyclic amines (Sawada et al, 1994). Also, the multiplicity of HAF in the HE group at 12 weeks was about 18-fold greater than that in the ME, although adduct levels in HE animals were about the same as the ME (Fig.…”

Section: 26mentioning

confidence: 65%

Nonlinearities in 2-Acetylaminofluorene Exposure Responses for Genotoxic and Epigenetic Effects Leading to Initiation of Carcinogenesis in Rat Liver

Williams¹

1998

Toxicological Sciences

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R. (1998). Toxicol. Sci. 45,[152][153][154][155][156][157][158][159][160][161] The dose responses for several effects of low-level limited exposures to 2-acetylaminofluorene (AAF) in the livers of male Fischer 344 rats were measured and a subsequent phenobarbital tumor promotion regimen was used to manifest initiation of carcinogenesis. Three doses over a 10-fold range yielding cumulative total exposures of 0.126,0.42, and 1.26 mmol AAF/kg body weight were achieved by daily intragastric instillation for up to 12 weeks with interim terminations. This was followed by 24 weeks administration of 500 ppm phenobarbital (PB) in the diet to promote liver tumor development. At 12 weeks at the end of AAF administration, all exposures produced adducts in liver DNA, measured by 32 P postlabeling, and the level of adducts increased with exposure, except that the high exposure did not produce a dose proportional increase. Measurement of arylsutfotransferase activity, a key enzyme in the metabolic activation of AAF, revealed that in livers from the high exposure animals, the enzyme was inhibited. To assess for toxicity, the centrilobular zone of glutamine synthetasepositive hepatocytes was quantified immunohistochemically at 12 weeks. The area of the zone was reduced in the high exposure group and there was a trend to reduction in relationship to exposure. The two lower exposures to AAF produced no increase in cell proliferation, whereas the high exposure resulted in a marked increase, about 8-fold over controls. Initiation was assessed by induction of hepatocellular altered foci (HAF) that expressed the placental form of glutathione 5-transferase. AAF induced HAF in the high exposure group, 9-fold at 8 weeks and 170-fold at 12 weeks compared to controls. In rats maintained on PB for 24 weeks after exposure, the multiplicity of HAF increased in controls and comparably in the low and mid exposure groups, but remained at the about the same high level in the high exposure group. The high exposure produced a substantial incidence of benign neoplasms by 12 weeks, and with promotion by 36 weeks, all rats developed hepatocellular neoplasia. In the mid exposure

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Section: 26mentioning

confidence: 65%

Nonlinearities in 2-Acetylaminofluorene Exposure Responses for Genotoxic and Epigenetic Effects Leading to Initiation of Carcinogenesis in Rat Liver

Williams¹

1998

Toxicological Sciences

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“…Heterocyclic amines [Trp-P-1, Trp-P-2, Glu-P-1, Glu-P-2, IQ, nitro-IQ, and MeIQx] induced chromosomal aberrations and sister-chromatid exchanges (94). We …”

Section: Attempts At Organ-speciˆc In Vivo Short-term Assays For the mentioning

confidence: 84%

“…Chromosomal Aberrations, Micronuclei, and Sister-chromatid Exchanges in the Rat Liver Chromosomal aberrations, micronuclei, and sisterchromatid exchanges were induced in rat liver with genotoxic hepatocarcinogens 2AAF and DMN but not with a non-genotoxic hepatocarcinogen CCl4 (93,94). Heterocyclic amines [Trp-P-1, Trp-P-2, Glu-P-1, Glu-P-2, IQ, nitro-IQ, and MeIQx] induced chromosomal aberrations and sister-chromatid exchanges (94).…”

Section: Attempts At Organ-speciˆc In Vivo Short-term Assays For the mentioning

confidence: 98%

Attempts at Organ-specific In Vivo Short-term Tests for Environmental Mutagens and Carcinogens in Rodent Liver and Stomach

Furihata

2013

Genes and Environment

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The primary motivation for conducting short-term tests for environmental mutagens and carcinogens has been to predict mutagens and/or carcinogens and to assess any associated risks. Organ-speciˆc in vivo short-term tests in rodents are valuable because chemical carcinogenesis is generally organ-speciˆc. I have attempted to develop various organ-speciˆc in vivo short-term tests mainly in rodent liver and stomach. Recently, our collaborative study group, Toxicogenomics/Japanese Environmental Mutagen Society･Mammalian Mutagenicity Study Group (JEMS･ MMS), attempted to use gene expression proˆling in in vivo short-term tests, conducted DNA microarrays to extract candidate marker genes, and later shifted to quantitative real-time PCR (qPCR) to proˆle the expression of selected genes. We successfully discriminated 8 genotoxic hepatocarcinogens from 4 non-genotoxic hepatocarcinogens by statistical analysis using principal component analysis (PCA) based on the gene expression proˆles for 12 genes (Aen, Bax, Btg2, Ccnf, Ccng1, Cdkn1a, Gdf15, Lrp1, Mbd1, Phlda3, Plk2, and Tubb2c) in mouse liver at 4 and 48 h following a single intraperitoneal administration of chemicals as determined by qPCR. More recently, we successfully performed a similar study in rat liver. Previously, my collaborators and I developed various organspeciˆc in vivo short-term test methods, including UDS (unscheduled DNA synthesis); RDS (replicative DNA synthesis) using a liquid scintillation counter in rat glandular stomach, forestomach, colon, and liver and hairless mouse epidermis; DNA single-strand scission (DSS); and ornithine decarboxylase assay (ODC) in rat glandular stomach on 62 compounds. Developing short-term tests that are helpful for the risk assessment of human mutagens and carcinogens would contribute to the development of ideal prediction methods.

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“…Thus, nitro-IQ may be present by photoactivation in airborne particles from cigarette smoke and frying meat, and humans are likely to be exposed to nitro-IQ. Nitro-IQ exhibits mutagenicity in bacterial systems (60)(61)(62) and genotoxic activities (63,64), as well as IQ.…”

Section: Heterocyclic Aminesmentioning

confidence: 99%

Role of Oxidative DNA Damage in Dietary Carcinogenesis

Hiraku

Murata

Kawanishi

2006

Genes and Environment

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Dietary factors are implicated in approximately 35% of cancers attributed to environmental factors. Although an extremely wide variety of dietary factors are considered to contribute to carcinogenesis, its precise mechanism remains to be clariˆed. We focused on the role of oxidative DNA damage in carcinogenesis mediated by various dietary factors. We investigated the mechanism of oxidative DNA damage induced by a) amino acid metabolites, in relation to carcinogenesis caused by protein intake and amino acid imbalance, b) heterocyclic amines formed during cooking meat andˆsh, c) sugar and hyperglycemiarelated aldehydes, d) carcinogens contained in fermented foods, such as urethane, e) phytoestrogens including soy iso‰avones, f) carcinogens in edible plants, such as caŠeic acid and isothiocyanate, g) food additives, such as potassium bromate and benzoyl peroxide. These dietary factors and their metabolites induced metal-mediated oxidative damage to DNA in human cultured cells and 32 P-labeled DNA fragments obtained from human cancer-relevant genes. On the basis of our results, it is concluded that polycyclic compounds, such as heterocyclic amines, can cause oxidative DNA damage, although they appear to mainly form DNA adduct. On the other hand, monocyclic and aliphatic compounds, such as amino acid metabolites and urethane, may mainly cause oxidative DNA damage whereas they do not appear to form DNA adduct. Soy iso‰avones may cause carcinogenesis through initiation via oxidative DNA damage caused by their metabolites and promotion via cell proliferation induced by themselves. In this review, we discuss the role of oxidative DNA damage as the common mechanism of dietary carcinogenesis.

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Cumulative effects of chromosome aberrations and sister chromatid exchanges in rat liver induced in vivo by heterocyclic amines

Cited by 13 publications

References 0 publications

Nonlinearities in 2-Acetylaminofluorene Exposure Responses for Genotoxic and Epigenetic Effects Leading to Initiation of Carcinogenesis in Rat Liver

Nonlinearities in 2-Acetylaminofluorene Exposure Responses for Genotoxic and Epigenetic Effects Leading to Initiation of Carcinogenesis in Rat Liver

Attempts at Organ-specific In Vivo Short-term Tests for Environmental Mutagens and Carcinogens in Rodent Liver and Stomach

Role of Oxidative DNA Damage in Dietary Carcinogenesis

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