6-Dimethylaminopurine and cyclohexamide are mutagenic and alter reproductive performance and intrauterine development in vivo.
The compounds 6-dimethylaminopurine (6-DMAP) and cyclohexamide (CHX) are currently used to stimulate the development of embryos produced by nuclear transfer in the production of cloned mammals with a great deal success. This study investigated the effects of 6-DMAP and CHX in vivo using biological assays to evaluate reproductive performance in females, teratogenesis, and mutagenesis. The results of this study demonstrated that the activating agents of oocyte cytoplasm, 6-DMAP and CHX, altered the reproductive performance of the experimental animals, as well as increased the rate malformations. In addition to these adverse effects, the administration of these compounds in pregnant females resulted in genotoxic and mutagenic toxicity, as determined by comet and micronucleus assays carried out in peripheral blood samples, respectively. Based on these findings and that alterations in DNA are important, morpho-functional teratogenesis and diminished embryonic viability, suggesting that 6-DMAP and CHX, which are utilized during the cloning of mammals, are responsible for the fact that embryos produced by nuclear transfer show low viability after implantation in utero or after birth because of congenital malformations and/or alterations in their DNA.
Programa de Pós-Graduação em Biologia Celular e Molecular, Instituto de Biociências de Rio Claro, Universidade Estadual Paulista, Rio Claro, SP, Brasil rodrigo.oliveira@ufms.br.
R J
RJ
Oliveira
Departamento de Biologia Geral, Universidade Estadual de Londrina, Londrina, PR, Brasil.
M S
MS
Mantovani
Centro de Estudos em Células-Tronco, Terapia Celular e Genética Toxicológica, Núcleo de Hospital Universitário, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brasil.
J R
JR
Pesarini
Centro de Estudos em Células-Tronco, Terapia Celular e Genética Toxicológica, Núcleo de Hospital Universitário, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brasil.
M O
MO
Mauro
Departamento de Biologia Geral, Universidade Estadual de Londrina, Londrina, PR, Brasil.
A F
AF
da Silva
Centro de Estudos em Nutrição e Genética Toxicológica, Centro Universitário Filadélfia, Londrina, PR, Brasil.
T R
TR
Souza
Programa de Pós-Graduação em Biologia Celular e Molecular, Instituto de Biociências de Rio Claro, Universidade Estadual Paulista, Rio Claro, SP, Brasil.
L R
LR
Ribeiro
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000818:Animals; D019976:Cloning, Organism; D003513:Cycloheximide / Q000009:adverse effects*; D004624:Embryo Transfer; D005260:Female; D051379:Mice; D009153:Mutagens / Q000009:adverse effects*; D011247:Pregnancy; D012098:Reproduction / Q000187:drug effects* / Q000235:genetics; D064793:Teratogenesis / Q000187:drug effects
D009153:Mutagens; C001020:N(6),N(6)-dimethyladenine; D003513:Cycloheximide; D000225:Adenine