Development of an experimental model of tumor growth under hypothyroidism

Abstract

Aim. Our aim has been to develop an experimental model of the tumor growth against the background of hypothyroidism in rats of both genders in order to study possible influence made by hypothyroidism on progression of malignant tumors of various histological types. Materials and methods. In our studies we have used 100 outbred albino rats of both genders, with an individual body mass of 150-180 g. The female rats (n=30) and the male rats (n=30) have received Mercazolil at a day dosage of 2,5 mg/100g of the body weight for 30 days. After hypothyroidism in the treated rodents had been confirmed, one group of them (15 females and 15 males) were subcutaneously inoculated with the Guerin’s carcinoma cells, and another group (covering other 15 females and other 15 males) has been undergone to transplantation of the Sarcoma 45 cells. The reference group has included the rats of both genders with subcutaneously inoculated the Guerin’s carcinoma cells (n=10 females and n=10 males) and Sarcoma 45 cells (n=10 females and n=10 males), but without reproduction of the hypothyroidism model. Upon expiration of one month, within the 3 day period, we have estimated with a radioisotope analysis (RIA) standard assay kits (Immunotech, Czekh Republic) the levels of the thyroid hormones in blood of the tested animals as follows: Triiodothyronine (T3) (pM/L), total Thyroxine (T4) (pM/L) and Thyroid-Stimulating Hormon (TSH) (μU/mL). The obtained data have been processed with Statistica 10.0. Results. Upon the treatment with Mercazolil, we have found in the females a decrease by a factor of 7,3 in the total level of Thyroxine and an increase by a factor 1,6 in the TSH level (p<0,05), while in the males we have recorded a reduction by a factor of 2 in the total level of Thyroxine and an increase by a factor of 1,5 in the TSH level (p<0,05). In this case, the average sizes of the tumors in the female rats with Guerin’s carcinoma and hypothyroidism have been found smaller than those found in the reference group as given below: upon expiration of 4 days they are 1,3 times smaller (p<0,05), upon expiration of 7 and 10 days the volumes have been found 1,4 times smaller (p<0,05); upon expiration of 14 days the volumes have been recorded to be 1,5 times less (p<0,05); upon expiration of 18 days they have been reported to be 1,3 times less (p<0,05), and upon expiration of 21 days they have been estimated to be 1,4 times less (p<0,05). As to the males with Guerin’s carcinoma and hypothyroidism, the average sizes of their tumors as against the reference group data have been recorded to be smaller as follows: upon expiration of 4 days they are found 13,3 times less; upon expiration of 7 days they have been recorded to be 7,5 times smaller; upon expiration of 10 days the volumes have been estimated to be 1,9 times less (p<0,05), and upon expiration of 14 days they have been found to be 2,6 times less. The survival rate in the female rats in the main test has been recorded to be 1,6 times higher (p<0,05) against the data in the reference group, while the survival rate in the males has not shown any significant differences therein. In the female rates with S 45 growing against the background of hypothyroidism the average sizes of the tumors have been found to be less than those identified in the reference group as follows: after 4 days, the sizes have been recorded to be 1,4 times less (p<0,05); after 7 and 10 days they have been recorded to be 1,6 and 3,2 times smaller, respectively (p<0,05); after 14 days they have been found to be 3,9 times less, and after 18 days they have been recorded to be 4,8 times less. In the males at tumor growth week stage 1, the tumor sizes have increased 3,1 times as against 4 days of the tumor growth; upon expiration of 10 days the sizes have been found to be 7,1 times greater as compared with the previous period; upon expiration of 2 weeks they have increased 1,5 times (p<0,05); upon expiration of 18 and 21 days the tumor sizes have been recorded to be greater by a factor of 2,3 and by a factor of 1,6, respectively (p<0,05). The life spans in the female rodents in the main test group has been reported to be longer by a factor of 1,8 (p<0,05) than it has been the case with the reference group, and the average life span in the males has reached 21 days. Conclusion. We have revealed that in the female rates diagnosed with hypothyroidism the sizes of the subcutaneous tumor nodes of Guerin’s carcinoma and S 45 show slower progression as against that recorded in the reference group, and the life span recorded in the above rodents has been found as significantly longer, while in the male rats with hypothyroidism we have observed an irregular, slower, progression of the tumor nodes of Guerin’s carcinoma and S 45 within the period of 14 days, but subsequently we have detected the same progression rate as it is the case with the reference group data.

Disorders in connections of the hypothalamic-pituitarygonadal axis in rats with Guerin’s carcinoma against the background of induced hypothyroidism

“…Previously, we found that induced hypothyroidism inhibited the growth of transplanted Guerin's carcinoma and increased life expectancy only in female rats, while in male rats, despite the fact that the size of the tumors was smaller at the initial stages, after 2 weeks of the experiment it was comparable with the parameters in the animals with the independent tumor growth, and no increase in life expectancy was observed [16,17]. An analysis of the content of hypothalamic Gn-releasing and pituitary tropic hormones LH, FSH and prolactin (PRL) in rats of both sexes is presented in Table 1 herein.…”

“…Since the HPT axis is associated with the reproductive system, and since we previously established the sex specificity of the effect of hypothyroidism on the growth of Guerin's carcinoma [16], it is of particular interest to study changes in the functioning of the HPG axis in animals of both sexes with Guerin's carcinoma growing against the background of a simulated thyroid hormone deficiency…”

Influence by hypothyroidism on the level of sex hormones in blood and their intracrine content in the tumor in rats with Guerin’s carcinoma

“…Previously, we found that in female rats, hypothyroidism slowed down the increase in the volume of primary tumors of Guerin's carcinoma and prolonged their life expectancy. In males, a slight slowdown in the tumor growth was noted only up to day 14 after inoculation, then the tumor grew rapidly, and its volume did not differ from that recorded in the reference group, and no increase in life expectancy was reported [9,10]. It was just during that period, upon expiration of 19 days of the tumor growth, when significant gender differences in the growth of Guerin's carcinoma were revealed by us, and studies of indicators in blood and tissues were carried out.…”

Changes in the functional activity of the hypothalamic-pituitaryadrenal axis in rats of both sexes with Guerin’s carcinoma against the background of hypothyroidism

“…Previously, we have shown that the growth of Guerin's carcinoma against the background of hypothyroidism in the females slows down that makes its impact on a prolongation in life spans, while inhibition of the tumor growth was revealed in the males only at the initial stages after the tumor cell transplantation, then the tumor progressed rapidly, and, as a result, the life spans did not differ from the respective indicators in the group with the normal state of the thyroid gland [10].…”

“…It is known that the growth of a malignant tumor has a significant and often sex-dependent effect on the body's regulatory axes [9]. Moreover we previously found that induced hypothyroidism had an inhibitory effect on the growth of Guerin's carcinoma and S45 sarcoma only in the females, but not in the males [10,11].…”