Interaction between Radiation and Cadmium or Mercury in Mouse Embryos during Organogenesis

Michel, Chantal; Balla, I

doi:10.1080/09553008714551301

Cited by 9 publications

(2 citation statements)

References 17 publications

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“…In our study (Naya ct al., 1992(Naya ct al., , 1994, intravenous treatment with NAC decrcascd the incidence of fetal mortality, cleft palate and abnormal palatal rugae induced by Cd. The Cd-induced teratogenicity and/or cmbryotoxicity werc protected by pretreatment with Cd itself, radiation or mercaptoacrylic acid (Semba el al., 1977;Ferm and Layton, 1979;Ferm and Hanlon, 1987;Michel and Balla, 1987). This protection against Cd tcratogcnicity seemed to bc duc to the induction of metallothionein (MT), a cadmium binding protein (De et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Effects of Glutathione and Related Compounds on Teratogenicity of 5‐Fluorouracil or Cadmium Hydrochloride in Mice*

Naya

Yasuda

1997

Congenital Anomalies

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Glutathione (GSH) is a tripeptide consisting of cysteine, glutamic acid and glycine, and plays an important role in detoxification reactions. In this report, we describe (1) the effects of the depleting agents of GSH such as diethylmaleate (DEM), phorone, and buthionine sulfoximine (BSO) on teratogenicity of 5‐fluorouracil (5‐FU) in mice, (2) the effects of GSH or N‐acetyl‐L‐cysteine (NAC), a precursor of GSH on teratogenicity of 5‐FU or cadmium hydrochloride (Cd) in mice. Pregnant ICR mice were injected intra‐peritoneally (i.p.) with 5‐FU at dose levels of 20, 25, and 30 mg/kg on day 11 of gestation (vaginal plug = day 0). Mice were injected i.p. with DEM, phorone, or BSO 4 to 6 hours before dosing with 5‐FU. Mice were also pretreated intravenously (i.v.) with GSH at dose levels of 150, 300 and 600 mg/kg, or NAC at dose levels of 80, 160, and 320 mg/kg 0.5 to 2 hours before dosing with 5‐FU. In the Cd‐teratogenicity study, mice were injected i.v. with GSH or NAC before dosing with Cd at 3.5 mg/kg i.p. on day 11 of gestation. Pretreatment with DEM, phorone or BSO increased the incidence of oligodactyly induced by 5‐FU, while pretreatment with GSH or NAC decreased the incidences. Pretreatment with GSH or NAC decreased the incidence of cleft palate and abnormal palatal rugae induced by Cd. The results suggest that cysteine plays a key role in the teratogenicity of 5‐FU or Cd in mice.

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Section: Discussionmentioning

confidence: 99%

Effects of Glutathione and Related Compounds on Teratogenicity of 5‐Fluorouracil or Cadmium Hydrochloride in Mice*

Naya

Yasuda

1997

Congenital Anomalies

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“…The Cd-induced teratogenicity andor embryotoxicity were protected by pretreatment with Cd itself, radiation or mercaptoacrylic acid (Semba et al, 1977;Ferm and Layton, 1979;Ferm and Hanlon, 1987;Michel and Balla, 1987). This protection against Cd teratogenicity seemed to be due to the induction of metallothionein (MT), a cadmium binding protein (De et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Effects of N‐acetyl‐L‐cysteine on Teratogenicity of Cadmium in Mice

Naya¹,

Shuto²,

Yasuda

1994

Congenital Anomalies

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Embryotoxicity and teratogenicity of cadmium (Cd) and modulation of its effects by N-acetyl-L-cysteine (NAC) were evaluated in mice. Pregnant ICR mice were intraperitoneally injected with 3.5 mgikg of CdC12 on day 10 or I 1 of gestation (vaginal plug = day 0). Pregnant mice were pretreated with 160 mgkg of NAC intravenously 2 hours before dosing with CdC12. Pregnant mice were killed on day 17 of gestation. Fetuses were examined for external malformations, especially limb malformations, cleft palate and abnormal palatal rugae. There was little difference in body weight gain of dams during the gestation period in the groups treated with NAC plus Cd as compared with the groups treated with Cd alone. Pretreatment with 160 mgkg of NAC decreased the fetal mortality, incidence of cleft palate and abnormal palatal rugae induced by Cd on day 11.On day 10, pretreatment with NAC decreased the incidence of Cd induced abnormal palatal rugae. These results clearly indicate that NAC exerts protective effects against embryotoxicity and teratogenicity of Cd.Glutathione (GSH), y-glutamylcysteinylglycine, is the most abundant nonprotein thiol in mammalian cells.It is known to be a major intracellular antioxidant, a key component in the metabolism of cysteine and cysteine-containing proteins, and a specific deactivator of potentially toxic electrophilic agents. A number of compounds have been developed to alter the metabolism and intracellular concentration of GSH. N-acetyl-L-cysteine (NAC), a precursor of cysteine, is able to penetrate the cell membrane, and intracellularly it is rapidly deacetylated to L-cysteine by N-acetylases present in different organs (Birnbaum et al., 1952). NAC is also known to increase the intracellular GSH levels in the liver, erythrocytes, and the lung (De Flora et al., 1985). The intracellular GSH levels in different cell systems can be decreased after treatment with diethylmaleate (DEM), D,L-buthionine-S-R-sulfoximine (BSO), and phorone (diisopropylidene acetone) (Meister, 1985).

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Interactions in developmental toxicology: A literature review and terminology proposal

Nelson

1994

Teratology

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Developmental toxicologists have investigated the interactive effects from concurrent exposures to a variety of chemical and physical agents, including therapeutic drugs, industrial agents, and some biological organisms or their toxins. Of approximately 160 reports of concurrent exposures reviewed in this paper, about one third report no interactive effects (including additive effects--usually referring to response--as opposed to dose-additivity); another one third report antagonistic effects, and the final third report potentiative or synergistic effects. The quality of the studies is highly variable. Frequently, only small numbers of animals were included, and very few dose levels were evaluated. Maternal toxicity was rarely discussed. Time-effect relationships were examined infrequently. In addition, these studies are also inconsistent in the use of terms to describe interactive effects, and more than 90% of the terms were not in harmony with currently accepted definitions in toxicology. Because interaction studies will continue to be important in the future, this paper proposes uniform usage of terms for additivity and interactions in developmental toxicology: additivity (the combined effect of two or more developmental toxicants approximates the sum of the effects of the agents administered separately); antagonism (the combined effect of two or more agents, one or more of which are present at doses that would be developmentally toxic if given individually, is significantly less than the sum of the effects of the agents administered separately); potentiation (the increased effect of a developmental toxicant by concurrent action of another agent at a dose that is not developmentally toxic); synergism (the combined effect of two or more developmental toxicants is significantly greater than the sum of the effects of each agent administered alone); and, interaction if more precise terminology does not apply.

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Interaction between Radiation and Cadmium or Mercury in Mouse Embryos during Organogenesis

Cited by 9 publications

References 17 publications

Effects of Glutathione and Related Compounds on Teratogenicity of 5‐Fluorouracil or Cadmium Hydrochloride in Mice*

Effects of Glutathione and Related Compounds on Teratogenicity of 5‐Fluorouracil or Cadmium Hydrochloride in Mice*

Effects of N‐acetyl‐L‐cysteine on Teratogenicity of Cadmium in Mice

Interactions in developmental toxicology: A literature review and terminology proposal

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