Comparison of micronuclei frequency in bone marrow cells of three rat lines.

The aim of this paper is to compare the spontaneous and induced with cyclophosphamide micronucleus indexes in bone marrow cells of the Sprague Dawley, Lewis and Wistar rat lines. Five experimental groups were formed (10 animals of each sex and of each line, in every group). The first group was used as the negative control (intact animals), the second one was exposed to oral administration of drugs; other conditions were the same as for the other groups. The third group was treated with 2% Tween 65 and the fourth group was treated with 0.9% NaCl. Both substances were administered by oral way to 2 ml/kg during 14 days. The fifth group was treated intraperitoneally with strong mutagen cyclophosphamide in the dose of 50 mg/kg (10 ml/kg in solution), on 48th and 24th hours before euthanasia. The Sprague Dawley line (both sexes) was significantly different from the other lines. Rats of this line had lower index of spontaneous formation of micronuclei, higher index of cyclophosphamide-induced micronucle formation, percent of micronucleated erythrocytes in bone marrow and the index of cytotoxicity. The results obtained make it possible to identify the most appropriate line of rats as model animals for studies of genotoxicity. It will allow also to obtain more accurate estimates of genotoxicity of various substances.

Respuesta de ratones Balb/c frente a ciclofosfamida y bleomicina en el ensayo cometa alcalino de linfocitos de sangre periférica / Balb/c mice response against cyclophosphamide and bleomycin in the alkaline comet assay of peripheral blood lymphocytes

En este artículo se evaluó el efecto mutágenico de la ciclofosfamida y bleomicina, con el objetivo de armonizar el número de exposiciones al ser utilizadas como controles positivos en ensayos in vivo de genotoxicidad, mediante el ensayo cometa alcalino. Se realizó en linfocitos de sangre periférica, utilizando 10 ratones/grupo/sexo de la línea Balb/c como biomodelo experimental. Fueron formados 5 grupos experimentales/sexo, el primero administrado con NaCl al 0,9% por vía intraperitoneal (i.p) como control negativo. El segundo y el tercero administrados con ciclofosfamida por vía i.p, con diseños de tratamientos diferentes en dosis de 50 mg/kg. El cuarto y quinto grupo fueron administrados con bleomicina por vía i.p, igualmente en dos diseños de tratamientos diferentes en dosis de 20 mg/kg. El mayor valor de inducción de daño se obtuvo con el uso de la ciclofosfamida y bleomicina, ambas en el diseño de administración de 48 y 24 horas antes de la eutanasia. Este estudio será aplicable a la evaluación de drogas que no han sido exploradas en el ámbito de la antigenotoxicidad y genotoxicidad in vivo. Además permitirá contar con un mayor conocimiento acerca de este ensayo, favoreciendo su validación (AU)

In this article were evaluated the mutagenic effect of cyclophosphamide and bleomycin, with the objective of harmonizing the number of exhibitions when being used as positive controls on in vivo genotoxicity assay, by means of alkaline comet assay. It was carried out in peripheral blood lymphocytes, using 10 mice/group/sex of the Balb/c line as experimental biomodel. We were formed 5 experimental groups per sex. The first group was administered with NaCl 0,9 % by intraperitoneal (i.p) route. The second and third groups were administered with cyclophosphamide by i.p route, with designs of different treatments at doses of 50 mg/kg. The fourth and fifth groups were administered with bleomycin by i.p route, equally in two designs of different treatments at doses of 20 mg/kg. The bigger inductions of damage were obtained with the use of the cyclophosphamide and bleomycin, both in the design of 48 and 24 hours administration before the euthanasia. This study will be applicable to the drugs evaluation that they have not been explored in to the in vivo antigenotoxicity and genotoxicity environment. It will also allow having a bigger knowledge about this assay, favoring their validation (AU)

Comparación de la respuesta de ratas Sprague Dawley frente a ciclofosfamida y bleomicina en el ensayo de la morfología de la cabeza del espermatozoide / Comparison of the Sprague Dawley rat’s response against cyclophosphamide and bleomycin in the head sperm morphology assay

El ensayo de la morfología de la cabeza del espermatozoide permite el estudio del potencialgenotóxico de muestras problemas a nivel celular, esta herramienta evalúa los cambios efectuados enla concentración espermática, así como el aumento de la frecuencia espontánea de cabezas deespermatozoides morfológicamente anormales. En este artículo decidimos evaluar y comparar en elbiomodelo de ratas Sprague Dawley machos, el efecto de dos sustancias mutagénicas en este ensayo,la Ciclofosfamida (CF) en dosis de 50 mg/kg y la Bleomicina (BL) en dosis de 30 mg/kg,administradas por vía intraperitoneal durante 5 días consecutivos, siendo sacrificados los animales 52días después de la última administración de los mutágenos. Se obtuvo como resultado que ambosmutágenos disminuyeron la concentración espermática y aumentaron el índice espontáneo de cabezasanómalas en los espermatozoides, siendo observado un marcado efecto mutagénico en la CF encomparación con la BL. Al final de la experiencia se obtuvieron mayores resultados de inducción decabezas de espermatozoides anómalas con el uso de la CF. Estos resultados reafirman el uso de estemutágeno como control positivo eficiente y seguro en este ensayo el cual se encuentra incluido en losestudios de genotoxicidad y toxicología de la fertilidad(AU)

The head sperm morphology assay, allows the study of the genotoxic potencial of samples at thecellular level problems; this tool to evaluate the spermatic concentration changes, as well as theincrease of the spontaneous heads frequency of sperms morphology abnormal. In this article we decideto evaluate and to compare in the Sprague Dawley males rats, the effect of two mutagenic substancesin these assay, the Cyclophosphamide, (CF) in dose of 50 mg/kg and the Bleomycin (BL) in dose of30 mg/kg, administered by intraperitoneal route during 5 consecutive days, being sacrificed theanimals 52 days after the last administration of the mutagens. It was obtained that both mutagendiminished the spermatic concentration and they increased the spontaneous index of anomaloussperms heads, being observed a marked mutagenic effect in the CF in comparison with the BL. At theend of the experience bigger results of induction of anomalous heads sperms were obtained with theuse of the CF. These results reaffirm the use of this mutagen as efficient and safe positive control inthis assay which is included in the genotoxicity studies and fertility toxicology(AU)