Sensitive stages for the production of developmental abnormalities in mice with 5‐fluorouracil

Dagg, C. P.

doi:10.1002/aja.1001060202

Cited by 103 publications

(24 citation statements)

References 12 publications

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“…It was chosen the period from the 9 th to the 13 th days of pregnancy, as long as it is the most important period to embryonic formation of structures of the rat head. DAGG (1960) refers that the 9 th day is very important for the formation of ocular structures. Our results can be considered concordant with this Author's finding.…”

Section: Discussionmentioning

confidence: 99%

“…Experimental studies in rodents, rabbits and monkeys have shown embryotoxic and teratological effects of antimitotic drugs. Studies have been carried out with 5-fluorouracil (DAGG, 1960;WILSON, 1971;SHAH and MACKAY, 1978;GRAFTON et al, 1987), adriamicyn and daunomicyn (THOMPSON et al, 1976), 3,3-dimethyl-1-phenyltriazene (FRANK et al, 1989. For further pharmacological references on antimitotic drugs, see CHABNER et al, (1996).…”

Section: Introductionmentioning

confidence: 99%

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Dental Germ Formation as Influenced by 5-Fluorouracil (5-Fu) in Newborn Rats

Rocha¹,

Bastos-Ramos²,

Filho³

et al. 1998

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-It was studied the influence of the antimitotic drug 5 -fluorouracil (5-FU), administered to pregnant rats, on dental germ formation of newborn rats. A total of 125 female aged 90-100 days and 15 male adult rats (Rattus rattus norvaegicus, albinus, Wistar) were used. The drug was injected intraperitoneally in single doses to females at the 9 th , 10 th , 11 th , 12 th and 13 th days of pregnancy. The animals were divided in four groups according to the doses administered: 10, 20, 30 and 40 mg/kg. Results show that the drug induced no toxicity to mothers, other than loss of body weight with higher doses (30-40 mg/kg), but caused in the fetuses dental germ anomalies and body external malformations. The proportion of such anomalies were, besides dose dependent, influenced by the day of pregnancy when the drug was administered to the mothers: there was a greater sensitivity at the 9 th day and a lesser one at the 10 th day. Higher doses (30-40 mg/kg) caused frequently embryonic death or fetal uterine reabsorption. Agenesia of the dental germ was frequently found.Key Words: antimitotic drugs; 5-fluorouracil; dental germ; fetal malformation.RESUMO -Foi estudada a influência da droga antimitótica 5-fluoruracil (5-FU), administrada a ratas prenhes sobre a formação do germe dental de ratos recém nascidos. Foram utilizadas 125 fêmeas com 90-100 dias de idade e 15 machos adultos (Rattus rattus norvaegicus, albinus, Wistar). A droga foi injetada por via intraperitoneal a ratas grávidas, em doses únicas, aos 9 º , 10 º , 11 º , 12 º ou 13 º dias de gestação. Os animais foram divididos em quatro subgrupos de acordo com a dose administrada: 10, 20, 30 e 40 mg/kg. Os resultados mostraram que nessas doses, o 5-FU não teve efeito tóxico nas ratas prenhes, alem de perda de peso com doses mais elevadas (30-40 mg/kg), enquanto causou anomalias dentais nos embriões, bem como malformações externas. A proporção de tais anomalias foi, alem de dose dependente, influenciada pelo dia de gestação no qual antimitótico foi administrado às mães: foi observada maior sensibilidade ao 9 º dia e menor ao 10 º dia. Doses mais elevadas (30-40 mg/kg) causaram freqüentemente morte do embrião e reabsorção fetal. Agenesia do germe dentário foi freqüentemente observada.Palavras-Chave: drogas antimitóticas; 5-fluorouracil; germe dentário; malformações fetais.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dental Germ Formation as Influenced by 5-Fluorouracil (5-Fu) in Newborn Rats

Rocha¹,

Bastos-Ramos²,

Filho³

et al. 1998

AVS

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“…5-Fluorouracil (5-FU) was selected for the test agent since it has been well documented as a consistent teratogen in rats [17], mice [4,12], hamster [11], and monkey [15]. However, the mechanism for the embryopathic effect of the drug is unknown.…”

Section: Methodsmentioning

confidence: 99%

A Comparison of the In Vivo and In Vitro Response of Rat Embryos to 5-Fluorouracil.

1998

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ABSTRACT. This study serves to further define the capabilities of the whole embryo culture system using the well-known teratogen, 5-fluorouracil (5-FU), an antineoplastic agent. An initial in vivo study was performed whereby pregnant rats were injected intraperitoneally with 10-30 mg/kg 5-FU on day 9 of gestation. On day 20 of gestation, the effects of this drug on the growth and development of embryos were evaluated. The number of externally malformed fetuses increased in a dose-related manner, and the most common defect was micro-/anophthalmos in fetuses of dams treated with 5-FU. Growth retardation was also noted in the 5-FU treated groups. An in vitro study was performed in which drug concentrations were varied (0.15-0.30 µg/ml). Externally abnormal embryos were observed in whole embryo culture system from embryonic day 9 to 11. The most common defect was hypoplastic optic vesicles. In the whole embryo culture system, crown-rump length, somite number, protein contents, and morphological score were decreased in a dose-dependent fashion. Finally, histological evaluation and observation of the pattern of cell death of the optic vesicle of 11-day-old embryos in in vivo and in vitro were performed. These parameters revealed no differences in response between in vivo and in vitro embryos treated with 5-FU, suggesting that the whole embryo culture system was an appropriate model for developmental toxicity studies of 5-FU. -KEY WORDS: cell death, 5-fluorouracil, histological evaluation, optic vesicle, whole embryo culture.J. Vet. Med. Sci. 60(1): 93-99, 1998 order to compare the development of the optic vesicle in vivo and in vitro. MATERIALS AND METHODSChemicals: 5-Fluorouracil (5-FU, Sigma Chemical Co., MO, U.S.A.) was dissolved in saline for treatment of pregnant females or dissolved in Tyrode's buffer (Sigma) for exposure of embryos. Methionine (Sigma) and D (+)-glucose anhydrous (E. Merck. AG., Darmstadt, Germany) were added to the culture medium.Animals: Sprague-Dawley spf rats (Charles River, Atsugi, Japan) were used under conditions of constant temperature (24 ± 1°C) and relative humidity (55 ± 5%), and a defined light-dark cycle (dark period from 7:00 P.M. to 7:00 A.M.). Food (CA-1, Clea, Japan) and water were provided ad libitum. Nine-week-old virgin females after being acclimatized for 1 week, were mated overnight with a male; the following morning was designated as day 0 of gestation if sperm were detected in the vaginal smear.Teratological evaluation: In utero experiment, at a defined time (12:00 A.M.) on day 9 of gestation, pregnant females were treated intraperitoneally with 5-FU at dose levels of 10, 15, 17, 20 and 30 mg/kg. Animals serving as the control received saline (5 ml/kg). All females were killed by deep ether anethesia and hysterectomized on day 20 of gestation. The number of early and late resorptions and viable fetuses was recorded. Viable fetuses were weighed, sexed, and examined for gross external malformations including abnormality of oral cavity under a dissecting microscope.In the...

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“…El 5 fluoracilo ha demostrado aumento de la supervivencia en el cáncer colorectal (10) aún no se dispone de estudios epidemiológicos en cuanto a anomalías congé-nitas en hijos de madres expuestas a dicho quimioterapéutico (15,16)young age or female sex. Experimental and epidemiological data suggest a protective effect of oestrogen against the induction of (intestinal, solo series de casos que muestran abortos en alrededor del 50% de las pacientes en primer trimestre y restricción del crecimiento intrauterine (RCIU) en segundo y tercer trimester lo que hace importante la vigilancia del crecimiento fetal en las gestantes que cursan con cáncer que require manejo con quimioterapia (17)(18)(19)(20) CASO CLÍNICO #1 Presentamos el caso de una paciente de 34 años G4P3 con gestación de 18 semanas y 3 días al ingreso remitida de un primer nivel de atención por cuadro clínico de un mes de evolución caracterizado por dolor lumbosacro izquierdo de intensidad progresiva, con impresión diagnóstica de urolitiasis, evidencia de anemia normocítica normocrómica con Hb 7.5 g/dL y ecografía renal y de vías urinarias institucional normal. La ecografía de abdomen total mostró hallazgos sugestivos de torsión ovárica izquierda sin abdomen quirúrgico en ese momento.…”

Section: Introductionunclassified

Endocarcinoma gástrico y embarazo reporte de dos casos y revisión de la literatura

et al. 2017

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RESUMENLa incidencia de cáncer durante la gestación es de 1: 1000 a 2000 embarazos, siendo los más frecuentes el de cérvix, mama, ovario, melanoma, tiroides, colon y hematológicos como linfoma y leucemia. A pesar de ser una entidad poco frecuente en el embarazo, se ha visto una tendencia a aumentar en los últimos años debido al incremento progresivo de la edad materna en el momento de la concepción.El carcinoma gástrico es una patología aún menos frecuente, siendo su incidencia durante la gestación de aproximadamente 0.016% a 0.026% en las series de casos de Japón, país con la mayor prevalencia de enfermedad. La cirugía es el tratamiento oncológico menos controversial durante la gestación. En los últimos años, ha cobrado importancia la quimioterapia adyuvante con antineoplásicos de tipo antimetabolito como el 5 fluoracilo (5 -FU), medicamento que ha demostrado mejoría de la supervivencia en pacientes gestantes con adenocarcinoma gástrico. Desafortunadamente, el 96.7% de los casos son diagnosticados en estadíos avanzados, pues su presentación clínica suele confundirse con las manifestaciones propias de la primera mitad de la gestación como son las nauseas y el vomito.Presentamos dos casos clinicos, el de una gestante de 34 años con embarazo de 19 semanas y 3 días al momento del diagnóstico de un carcinoma gástrico Bormann III, llevada a laparotomía con intención curativa a las 21 semanas con hallazgo intraoperatorio de enfermedad metastásica avanzada y tumor ovárico izquierdo sugestivo de tumor de Krukenberg, a quien se le inicia a las 23 semanas quimioterapia paliativa con esquema FOLFIRI el cual recibió hasta la finalización de la gestación a las 33 semanas por restricción del crecimiento intrauterino y posteriormente durante el puerperio; y el de una gestante de 31 años con embarazo de 26 semanas y 6 días quien se ingresa para estudio de emesis persistente durante la gestación con confirmación diagnóstica de adenocarcinoma gástrico Bormann III asociado a Restricción del crecimiento intrauterino que fue llevada a cesárea a las 34 semanas y en el puerperio a gastrectomía total con vaciamiento ganglionar del area celiaca y reconstrucción en Y de Roux.

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Sensitive stages for the production of developmental abnormalities in mice with 5‐fluorouracil

Cited by 103 publications

References 12 publications

Dental Germ Formation as Influenced by 5-Fluorouracil (5-Fu) in Newborn Rats

Dental Germ Formation as Influenced by 5-Fluorouracil (5-Fu) in Newborn Rats

A Comparison of the In Vivo and In Vitro Response of Rat Embryos to 5-Fluorouracil.

Endocarcinoma gástrico y embarazo reporte de dos casos y revisión de la literatura

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