Periodontal ligament hyalinization in an experimental model of lathyrism

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S230 Abstracts / Toxicology Letters 172S (2007) S1–S240 deoxyguanosine (8-oxo-dG) in female rat liver DNA. It has been postulated that estrogens can act as geno- toxic procarcinogens. Particularly, the 17--estradiol (E2) catechol metabolite 4-hydroxyestradiol formed by CYPs, can undergo redox cycling and thus generate DNA damaging reactive oxygen species (ROS) and the corresponding quinone may cause DNA damage. We have shown that induction of CYPs by TCDD (1 nM) was able to increase ROS formation in rodent but not in human HepG2 hepatoma cells. Co-incubation of TCDD with E2 (100 nM) did not markedly enhance TCDD-induced ROS formation measured using the 2 ,7 -dihydrodichlorofluorescein diacetate (H 2 DCFDA) fluorescence assay. In addition, real-time RT-PCR anal- ysis following treatment of TCDD and E2 in HepG2 and rat H4IIE hepatoma cells will provide further infor- mation on CYP1A1 and CYP1B1 mRNA expression. Utilizing the single-cell gel electrophoresis (Comet) assay we observed no increase in DNA strand breaks in HepG2 and H4IIE cells exposed to TCDD (up to 100 nM) or E2 (1–100 nM) for 20 and 48 h. doi:10.1016/j.toxlet.2007.05.578 Z22 Periodontal ligament hyalinization in an experimental model of lathyrism Pedro Gomes 1 , Ana G. da Fonseca 1 , Rodrigo Farinha Farinha 1 , Fernando Capela e Silva 2 , Ant´ onio Ramos 3 , Ant´ onio M. Silv´ erio Cabrita 3 1 Health Sciences Department of Viseu—UCP, Viseu, Portugal; 2 Biology Depatment of Evora University, ` Evora, Portugal; 3 Institute of Experimental Pathology—Fac, Medicine of Coimbra, Coimbra, Portugal Lathyrism is a disease characterized by impairment of crosslinking of collagen molecules. We evaluated the morphologic changes in periodontal ligament in an experimental model of a lathyrism. Thirty Wistar male rats, were randomly distributed by three groups of ten animals each. Group I was submitted to no manipulation. Groups II and III was submitted to the administration of hydrochloride semicarbazide for 4 weeks. The toxic was incorporated in the diet in the dose of 3 g/kg for group II and 6 g/kg for group III. The animals were sacrificed on the 30th day. Areas occupied by hyaline material (Hy) within periodontal ligament (PL) were observed, calculated and presented as a ratio (R): Hy/PL at a infra-coronal pulp level of the first mandibular molar. This relation is 0 in the control group. According to the median Hy/PL and the SD, in the groups II, were considered the following groups: median Hy/PL, high Hy/PL and low Hy/PL. The percentage cases of Hy/PL in the group II was low Hy/PL, 22%; median Hy/PL, 56%; high Hy/PL, 22%. The percentage cases of Hy/PL in the group III was low Hy/PL, 15.38%; median Hy/PL, 61.54%; high Hy/PL, 23.08%. The results suggest that the lathyrism produced char- acteristic lesions in the periodontal ligament, which are seen in a higher frequency when the concentration of lathyric agent is increased. doi:10.1016/j.toxlet.2007.05.579 Z23 Repeated dose subcutaneous administration of 1E10 vaccine in Sprague–Dawley rats Yana Gonz´ alez 1 , Ana Bada 1 , B´ arbara Gonz´ alez 1 , Osvaldo Hern´ andez 1 , Juana Hern´ andez 1 , Dasha Fuentes 1 , Mar´ ıa Arteaga 1 , Ana V´ asquez 2 , Angel Casac´ o 2 1 CENPALAB, Ciudad Habana, Cuba; 2 CIM, Ciudad Habana, Cuba Cancer has become a serious problem for mankind because of its high incidence and mortality. Specific active immunotherapy is a therapeutic approach against this disease, allowing the targeting of immune response against malignant cells with a higher grade of effective- ness. The objective of this work was to determine the possible toxic effects due to the repeated dose subcu- taneous administration for 14 days of the therapeutic vaccine 1E10. It was established three groups of five Sprague–Dawley rats per sex: control (saline), vehicle (Alumina Gel) and treated (1E10 vaccine). Animals were daily observed to detect toxicity signs, and rectal temper- ature was measured before and after the administration of the substances. There were carried out haematolog- ical and blood chemistry exams on all animals at the beginning and at the end of the assay, and histopatholog- ical examination was performed on day 14th. There were not detected any significant variations neither in corporal weight nor rectal temperature or haematology parame- ters. Blood chemistry analysis showed an increased of bilirubin and creatinine in all groups, not been associ- ated to the vaccine administration. Animals of vehicle and treated groups showed multiple white ring-shaped formations in the subcutaneous cellular tissues at the administration site, possible due to the action of the

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Letters

S230 Abstracts / Toxicology

deoxyguanosine (8-oxo-dG) in female rat liver DNA.It has been postulated that estrogens can act as geno-toxic procarcinogens. Particularly, the 17-�-estradiol(E2) catechol metabolite 4-hydroxyestradiol formed byCYPs, can undergo redox cycling and thus generateDNA damaging reactive oxygen species (ROS) and thecorresponding quinone may cause DNA damage. Wehave shown that induction of CYPs by TCDD (1 nM)was able to increase ROS formation in rodent but notin human HepG2 hepatoma cells. Co-incubation ofTCDD with E2 (100 nM) did not markedly enhanceTCDD-induced ROS formation measured using the2′,7′-dihydrodichlorofluorescein diacetate (H2DCFDA)fluorescence assay. In addition, real-time RT-PCR anal-ysis following treatment of TCDD and E2 in HepG2and rat H4IIE hepatoma cells will provide further infor-mation on CYP1A1 and CYP1B1 mRNA expression.Utilizing the single-cell gel electrophoresis (Comet)assay we observed no increase in DNA strand breaks inHepG2 and H4IIE cells exposed to TCDD (up to 100 nM)or E2 (1–100 nM) for 20 and 48 h.

doi:10.1016/j.toxlet.2007.05.578

Z22Periodontal ligament hyalinization in anexperimental model of lathyrism

Pedro Gomes 1, Ana G. da Fonseca 1, Rodrigo FarinhaFarinha 1, Fernando Capela e Silva 2, Antonio Ramos 3,Antonio M. Silverio Cabrita 3

1 Health Sciences Department of Viseu—UCP, Viseu,Portugal; 2 Biology Depatment of Evora University,Evora, Portugal; 3 Institute of ExperimentalPathology—Fac, Medicine of Coimbra, Coimbra,Portugal

Lathyrism is a disease characterized by impairmentof crosslinking of collagen molecules. We evaluatedthe morphologic changes in periodontal ligament in anexperimental model of a lathyrism.

Thirty Wistar male rats, were randomly distributed bythree groups of ten animals each. Group I was submittedto no manipulation. Groups II and III was submittedto the administration of hydrochloride semicarbazidefor 4 weeks. The toxic was incorporated in the diet inthe dose of 3 g/kg for group II and 6 g/kg for groupIII. The animals were sacrificed on the 30th day. Areas

occupied by hyaline material (Hy) within periodontalligament (PL) were observed, calculated and presentedas a ratio (R): Hy/PL at a infra-coronal pulp level of thefirst mandibular molar.

172S (2007) S1–S240

This relation is 0 in the control group. According tothe median Hy/PL and the SD, in the groups II, wereconsidered the following groups: median Hy/PL, highHy/PL and low Hy/PL.

The percentage cases of Hy/PL in the group II was lowHy/PL, 22%; median Hy/PL, 56%; high Hy/PL, 22%.The percentage cases of Hy/PL in the group III was lowHy/PL, 15.38%; median Hy/PL, 61.54%; high Hy/PL,23.08%.

The results suggest that the lathyrism produced char-acteristic lesions in the periodontal ligament, which areseen in a higher frequency when the concentration oflathyric agent is increased.

doi:10.1016/j.toxlet.2007.05.579

Z23Repeated dose subcutaneous administration of 1E10vaccine in Sprague–Dawley rats

Yana Gonzalez 1, Ana Bada 1, Barbara Gonzalez 1,Osvaldo Hernandez 1, Juana Hernandez 1, DashaFuentes 1, Marıa Arteaga 1, Ana Vasquez 2, AngelCasaco 2

1 CENPALAB, Ciudad Habana, Cuba; 2 CIM, CiudadHabana, Cuba

Cancer has become a serious problem for mankindbecause of its high incidence and mortality. Specificactive immunotherapy is a therapeutic approach againstthis disease, allowing the targeting of immune responseagainst malignant cells with a higher grade of effective-ness. The objective of this work was to determine thepossible toxic effects due to the repeated dose subcu-taneous administration for 14 days of the therapeuticvaccine 1E10. It was established three groups of fiveSprague–Dawley rats per sex: control (saline), vehicle(Alumina Gel) and treated (1E10 vaccine). Animals weredaily observed to detect toxicity signs, and rectal temper-ature was measured before and after the administrationof the substances. There were carried out haematolog-ical and blood chemistry exams on all animals at thebeginning and at the end of the assay, and histopatholog-ical examination was performed on day 14th. There werenot detected any significant variations neither in corporalweight nor rectal temperature or haematology parame-ters. Blood chemistry analysis showed an increased ofbilirubin and creatinine in all groups, not been associ-

ated to the vaccine administration. Animals of vehicleand treated groups showed multiple white ring-shapedformations in the subcutaneous cellular tissues at theadministration site, possible due to the action of the