10/08/2008

Toxicity and Safety - Reproduction and post-natal toxicity - Special tests

• Effect of P-MAPA on Intra-ocular Graft Tooth Germ Development

 

The objective of this test was to verify the possible teratogenic effect of P-MAPA on intra-ocular grafts of tooth germ development of the two lower molar teeth of mice foetuses transplanted into the anterior chamber of the eyes of adult hosts.

 

This process is impaired by the use of teratogenic drugs.

 

Experimental protocol

 

Germs of molar teeth of 14 and 17 days of intrauterine life of mice foetuses were used. Germs were septically dissected and maintained in culture medium until grafted to the anterior chamber of the adult mouse host of the same strain.

 

The treated animals received 30 mg/kg of body weight of P-MAPA, intraperitoneal during 7 or 9 days and then were sacrificed. The eyes were removed for histological analysis. A verification of the quality of the germs was carried out previously to the graft.

 

Results

 

The 14 days tooth germs showed all their characteristic structural elements.

 

The dental pulp as a soft connective tissue with blood vessels and odontoblastic layer as differentiated cells in the occlusal areas.

 

A thin layer of dentin was seen. The ameloblast appeared as long cells and fibres with a parallel distribution around it.

 

Bony tissue was present around the tooth germ in a reasonable amount.

 

The 17 days tooth germs showed all their characteristic structures with thick layers of dentin and enamel, thinner in direction to cervical region.

 

Very little bony tissue was found around the tooth germ.

 

Despite the high P-MAPA dose used, no developmental changes of the tooth germs was found either with 14 or 17 days grafted in the anterior chamber of the eye of host animal.

 

The only difference which could be considered was that the treated animals exhibited mineralization tissues thinner than the control animals.

 

Conclusions : 

 

• These results showed a slight anabolic effect of P-MAPA, without any cytotoxic or cytostatic effect on this cellular system.

 

 •In spite of the high dose used in this experiments that is many times the therapeutic doses, the P-MAPA did not produce any interference on the  development of the structures analyzed of the foetuses.