title: Genotoxicity and cytotoxicity assessment of new ethyl-carbamates with ixodicidal activity.
abstract: The mammalian erythrocyte micronucleus test was used on the peripheral blood of Wistar rats exposed to two new ethyl-carbamates: ethyl-4-bromophenyl-carbamate (LQM 919) and ethyl-4-chlorophenyl-carbamate (LQM 996) to analyze their genotoxic potential. The mitotic index and cell proliferation kinetics in human lymphocyte cultures in the presence of these ethyl-carbamates were used to evaluate cytotoxicity and cytostaticity respectively. Exposure to greater acute doses (300mg/kg) and to all of the subchronic doses (12.5, 25 and 50mg/kg daily for 90 days) of these ethyl-carbamates induced an increased frequency (p<0.05) of micro-nucleated polychromatic erythrocytes (MN-PCE) compared with rats not exposed to the ethyl-carbamates. Increases in MN-PCE was higher in males than in females exposed to LQM 996 50mg/Kg (p<0.05). All observed changes in rats return 21days after suspending ethyl-carbamate exposure. The highest concentration (0.3mM) of both ethyl-carbamates in lymphocyte cultures increased the percentage of cells in first division metaphase and decreased the percentage of cells in third division metaphase, indicating an increase in cell cycle length or a possible cell cycle arrest in metaphase (cytostatic effect). The results of this study show that the evaluated ethyl-carbamates may induce genotoxic damage in rats and alterations in the human lymphocyte cell cycle.
authors.affiliation: Departamento de Ciencias Biológicas, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Mexico. Electronic address: mgpo1@hotmail.com.
authors.forename: María Guadalupe
authors.initials: MG
authors.lastname: Prado-Ochoa
authors.affiliation: Departamento de Ciencias Biológicas, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Mexico. Electronic address: mmunoz74@hotmail.com.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Muñoz-Guzmán
authors.affiliation: Laboratorio de Química Medicinal, Departamento de Ciencias Químicas, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Mexico. Electronic address: hugounam83@gmail.com.
authors.forename: Víctor Hugo
authors.initials: VH
authors.lastname: Vázquez-Valadez
authors.affiliation: Laboratorio de Química Medicinal, Departamento de Ciencias Químicas, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Mexico. Electronic address: velzquezanamara@gmail.com.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Velázquez-Sánchez
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico. Electronic address: anamsm@biomedicas.unam.mx.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Salazar
authors.affiliation: Departamento de Ciencias Biológicas, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Mexico. Electronic address: ramireznoguera@unam.mx.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ramírez-Noguera
authors.affiliation: Laboratorio de Química Medicinal, Departamento de Ciencias Químicas, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Mexico. Electronic address: eupirne@gmail.com.
authors.forename: Enrique
authors.initials: E
authors.lastname: Angeles
authors.affiliation: Departamento de Ciencias Biológicas, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Mexico. Electronic address: fealba@hotmail.com.
authors.forename: Fernando
authors.initials: F
authors.lastname: Alba-Hurtado
mesh_terms: D056810:Acaricides / Q000138:chemical synthesis / Q000633:toxicity*; D000818:Animals; D002219:Carbamates / Q000138:chemical synthesis / Q000633:toxicity*; D002478:Cells, Cultured; D054697:Cytostatic Agents / Q000138:chemical synthesis / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D009153:Mutagens / Q000138:chemical synthesis / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D014520:Urethane / Q000138:chemical synthesis / Q000633:toxicity*
chemical_list: D056810:Acaricides; D002219:Carbamates; D054697:Cytostatic Agents; D009153:Mutagens; C000614109:ethyl-4-bromophenyl-carbamate; C000614110:ethyl-4-chlorophenyl-carbamate; D014520:Urethane
keywords: Anti-tick activity; Carbamates; Micronucleus; Mitotic index; Rhipicephalus microplus