Forestomach tumor induction by 2,4-hexadienal in F344N rats and B6C3F1 mice

Chan, Po-Chuen; Mahler, Joel F.; Peddada, Shyamal D.; Lomnitski, Liat; Nyska, Abraham

doi:10.1007/s00204-003-0481-8

Cited by 8 publications

(7 citation statements)

References 32 publications

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“…In general, N CdIr , N Ir and N Cd were larger than N C . In all 12 sets of experiments, the N Cd values were significantly larger than the N C values, which agreed with the findings of Chan and Cheng [19]. In 11 out of the 12 sets of experiments, the N CdIr values were significantly larger than both the N Ir and N Cd values.…”

Section: Resultssupporting

confidence: 88%

“…The same stock solution was used for all experiments in the present project. It was established that significant amounts of apoptotic cells were observed in zebrafish embryos after exposure to 100 µM Cd from 5 to 28 hpf [19], which was commensurate with other tissue-culture studies using micromolar Cd concentrations [20][21][22][23][24]. Chan and Cheng [19] also found 0.67% of apoptotic cells by flow cytometry assay for embryos which were exposed to 1 µM Cd for 24 h. With reference to these results and to the literature, they concluded that ectopic induction of apoptosis only occurred for Cd exposures with higher concentrations [19].…”

Section: Cadmium Exposurementioning

confidence: 99%

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The multiple stressor effect in zebrafish embryos from simultaneous exposure to ionising radiation and cadmium

Choi

Lam

et al. 2013

J. Radiol. Prot.

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Living organisms are exposed to a mixture of environmental stressors, and the resultant effects are referred to as multiple stressor effects. In the present work, we studied the multiple stressor effect in embryos of the zebrafish (Danio rerio) from simultaneous exposure to ionising radiation (alpha particles) and cadmium through quantification of apoptotic signals at 24 h postfertilisation (hpf) revealed by vital dye acridine orange staining. For each set of experiments, 32-40 dechorionated embryos were deployed, which were divided into four groups each having 8-10 embryos. The four groups of embryos were referred to as (1) the control group (C), which received no further treatments after dechorionation; (2) the Cd-dosed and irradiated group (CdIr), which was exposed to 100 μM Cd from 5 to 24 hpf, and also received about 4.4 mGy from alpha particles at 5 hpf; (3) the irradiated group (Ir), which received about 4.4 mGy from alpha particles at 5 hpf; and (4) the Cd-dosed group (Cd), which was exposed to 100 μM Cd from 5 to 24 hpf. In general, the CdIr, Ir and Cd groups had more apoptotic signals than the C group. Within the 12 sets of experimental results, two showed significant synergistic effects, one showed a weakly synergistic effect and nine showed additive effects. The multiple stressor effect of 100 μM Cd with ~4.4 mGy alpha-particle radiation resulted in an additive or synergistic effect, but no antagonistic effect. The failure to identify significant synergistic effects for some sets of data, and thus their subsequent classification as additive effects, might be a result of the relatively small magnitude of the synergistic effects. The results showed that the radiation risk could be perturbed by another environmental stressor such as a heavy metal, and as such a realistic human radiation risk assessment should in general take into account the multiple stressor effects.

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Section: Resultssupporting

confidence: 88%

Section: Cadmium Exposurementioning

confidence: 99%

The multiple stressor effect in zebrafish embryos from simultaneous exposure to ionising radiation and cadmium

Choi

Lam

et al. 2013

J. Radiol. Prot.

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“…The National Toxicology Program (NTP) conducted studies of the toxicity and carcinogenicity of 2,4-hexadienal (hexadienal; Chan et al, 2003; National Toxicology Program, 2003). Like hexenal, hexadienal is found in foods as a natural and artificial component and is generally regarded as safe.…”

Section: Discussionmentioning

confidence: 99%

“…Crotonaldehyde induced gastric, respiratory, and hepatic toxicity and hepatic carcinogenesis (Chung et al, 1986; Wolfe et al, 1987). 2,4-Hexadienal induced gastric toxicity and carcinogenesis (Chan et al, 2003; National Toxicology Program, 2003). Many of the toxic effects of hexenal and other α, β-unsaturated aldehydes were observed at the site of contact; these effects are suggestive of local tissue irritation as an important mode of action.…”

Section: Introductionmentioning

confidence: 99%

Toxicity, DNA Binding, and Cell Proliferation in Male F344 Rats following Short-term Gavage Exposures to Trans-2-Hexenal

Stout¹,

Bodes²,

Schoonhoven

et al. 2008

Toxicol Pathol

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Hexenal is a genotoxic compound to which humans are exposed daily through the consumption of foods and beverages. The present studies were conducted to examine the relationships between the dose-responses of trans-2-hexenal-induced toxicity, DNA adduct formation, and cell proliferation. Male F344 rats were exposed by gavage to single doses of up to 500 mg/kg and killed 1, 2, or 4 days after dosing or were exposed to repeat doses of up to 100 mg/kg once daily for 5 days or 5 days per week for 4 weeks and killed 1 day after the end of the dosing period. Histologically, the primary observations were necroulcerative lesions, inflammation, and hyperplasia in the forestomach and inflammation in the glandular stomach. Hexenal-derived DNA adduct formation and cell proliferation were induced in the forestomach at doses of hexenal that also induced gastric toxicity; DNA adducts were not observed in the glandular stomach. These findings suggest that the toxicity of hexenal was limited to the site of contact (stomach) and that the observed DNA adduct formation and cell proliferation occurred in the setting of severe tissue damage.

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“…The effect of such Cd concentrations on zebrafish embryos was studied by Chan and Cheng (2003) who concluded that ectopic apoptosis was only induced for Cd exposures at higher concentrations. Significant numbers of apoptotic cells in zebrafish embryos which had been exposed to 100 µM Cd from 5 to 28 hpf were observed by Chan and Cheng (2003), while only 0.67% of apoptotic cells were found in zebrafish embryos exposed to 1 µM Cd for 24 h. Their data were commensurate with other tissue culture studies using Cd at micromolar ranges. Cd-induced apoptosis was reviewed by Robertson and Orrenius (2000).…”

Section: Discussionmentioning

confidence: 99%

Adaptive response to ionising radiation induced by cadmium in zebrafish embryos

Choi

Kong

et al. 2013

J. Radiol. Prot.

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An adaptive response is a biological response where the exposure of cells or animals to a low priming exposure induces mechanisms that protect the cells or animals against the detrimental effects of a subsequent larger challenging exposure. In realistic environmental situations, living organisms can be exposed to a mixture of stressors, and the resultant effects due to such exposures are referred to as multiple stressor effects. In the present work we demonstrated, via quantification of apoptosis in the embryos, that embryos of the zebrafish (Danio rerio) subjected to a priming exposure provided by one environmental stressor (cadmium in micromolar concentrations) could undergo an adaptive response against a subsequent challenging exposure provided by another environmental stressor (alpha particles). We concluded that zebrafish embryos treated with 1 to 10 μM Cd at 5 h postfertilisation (hpf) for both 1 and 5 h could undergo an adaptive response against subsequent ~4.4 mGy alpha-particle irradiation at 10 hpf, which could be interpreted as an antagonistic multiple stressor effect between Cd and ionising radiation. The zebrafish has become a popular vertebrate model for studying the in vivo response to ionising radiation. As such, our results suggested that multiple stressor effects should be carefully considered for human radiation risk assessment since the risk may be perturbed by another environmental stressor such as a heavy metal.

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Forestomach tumor induction by 2,4-hexadienal in F344N rats and B6C3F1 mice

Cited by 8 publications

References 32 publications

The multiple stressor effect in zebrafish embryos from simultaneous exposure to ionising radiation and cadmium

The multiple stressor effect in zebrafish embryos from simultaneous exposure to ionising radiation and cadmium

Toxicity, DNA Binding, and Cell Proliferation in Male F344 Rats following Short-term Gavage Exposures to Trans-2-Hexenal

Adaptive response to ionising radiation induced by cadmium in zebrafish embryos

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