The Effect Of Iodine Excess And Bisphenol A On Thyroid Neoplasms

BACKGROUNDThyroid carcinoma is the most common malignant tumor of the endocrine system. Epidemiological data suggests that the incidence of thyroid tumor in areas with high iodine intake is significantly increased. Bisphenol A (BPA) is one of environmental endocrine disruptors (EEDS). A large number of studies show that BPA has estrogenic activity. Therefore, we suppose that it may play an important role in the development of thyroid neoplasms. So, it is very necessary to study the effect of iodine excess and bosphenol A on thyroid neoplasms in animals.OBJECTIVETo analyze the effect of iodine excess and bisphenol A on thyroid cancer. To explore the pathogenesis of thyroid tumor, and may provide the experiment basis for the application of iodine and the BPA products.METHODSFour weeks female F344 rats were randomly assigned to injection N-bis (2-hydroxypropyl) nitrosamine (DHPN) group (DA group,60 rats) and non DHPN group (DN group,50 rats). According to different dose of BPA and potassium iodide, DN group divided to 5 groups:control group, BPA 250μg/kg (BPA250) group, BPA250μg/kg+KI 1000μg/L (BPA250+KI) group, BPA1000μg/kg (BPA1000) group, BPA1000μg/kg+KI 1000μg/L (BPA1000+KI) group,10 rats per group. DA group divided to six groups, one was KI 1000μg/L (KI) group, the other five were the same as DN group,10 rats per group. Rats were killed after 16 months, the serum samples were collected for testing FT3, FT4, TSH levels. Separating thyroid, fixed in the formalin after weighing, paraffin sections were cut at 4 μm and stained with hematoxylin and eosin, observed under Olympus light microscope by professional pathologists, analyzed the type and ncidence rate of thyroid tumors. Immunohistochemical SP method was used to detect the expression of PCNA in thyroid tissue of each group; qualitative analysis was investigated using the Image Pro Plus6.0 software. Data processing and statistical analysis use SPSS 19.0 statistical analysis package. The enumeration data using Fisher exact test, the difference of measurement data among the groups were analyzed by homogeneity test of variances, t-test and LSD method was used under an equal condition, otherwise the equivalent non-parametric test will be used.RESULTS1. The general condition of rats (hair, activity state, weight etc.)Treatment observation, injection of DHPN group compared with non DHPN group, reduce the average amount ingestion and water intake and decrease the average weight obviously, the hair color yellow and shiny.2. The average weight of ratsDN control group has the largest average weight, with significant difference compared with DA control group (P<0.05). Differences between the other groups were no statistically significant (P<0.05).3. The relative mass of thyroid gland of ratsIn DA group, the maximum relative quality of thyroid is KI group, while the minimum is the blank control group, with significant difference(P< 0.05); BPA group thyroid relative quality were greater than non BPA group, BPA+KI group relative quality were greater than BPA group, no significant difference.4. The incidence of thyroid tumor and type of ratsThe thyroid tumor type of DA+KI group is follicular thyroid adenoma, while the rest tumors in other groups are malignant tumors. In DN group, each of BPA+KI groups had 1 cases of carcimoma. In DA group, all groups have carcinoma occurrence except BPA250 group; while BPA250+KI group have the most number of carcinoma.5. Serum FT3、FT4 and TSH of ratsTSH levels were significantly elevated of KI group compared with control group. BPA group have no obvious difference to the control. while the groups giving BPA and KI have the higher FT3、FT4 and the lower TSH to the control, with significant difference.6. Positive rate and scores of thyroid PCNA immunohistochemistry of ratsIn all group, the highest positive rate was the DA group BPA250+KI group (90%), no statistically significant difference between the groups. Comparison of PCNA scores, the highest average score is DA group BPA+KI group, normal control group was the lowest, with significant difference (P<0.05); BPA 1000 +KI group of average score higher than the control group, no significant difference; KI group has the higher average score than the control group, with significant difference.CONCLUSION1. DHPN has an adverse impact on growth and life activities of rats, and has the oncogenicity effect on thyroid.2. Iodine excess could promote the proliferation of thyroid tissue in rats, and the effect on oncogenicity of thyroid need the further study.3. The effect of BPA alone promoting the proliferation of thyroid tissue and oncogenicity of thyroid are not obvious.4. In injection of DNPN, BPA and iodine combined in a certain concentration range can promote the proliferation of thyroid.5. Iodine excess could cause thyroid dysfunction; BPA seems to be no effect. While BPA and iodine combined may cause the thyroid hormone level changes.6. The genesis of thyroid neoplasms is not the result of the action of a single factor. The combined action of bisphenol A and iodine excess may promote the occurrence of thyroid tumors in rats.