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Son
Pronounced synergistic promotion of N-bis(2-hydroxypropyl)nitrosamine-initiated thyroid tumorigenesis in rats treated with excess soybean and iodine-deficient diets.Nishikawa A, Ikeda T, Son HY, Okazaki K, Imazawa T, Umemura T, Kimura S, Hirose M. Toxicol Sci. 2005 Aug;86(2):258-63. Epub 2005 May
18. "We have reported that excess soybean treatment and iodine deficiency synergistically interact, resulting in remarkable induction of thyroid hyperplasias in rats. In the present study, modifying effects of excess soybean and iodine-deficient diets were investigated in the post-initiation phase of N-bis(2-hydroxypropyl)nitrosamine [DHPN]-initiated thyroid tumorigenesis in rats. AIN-93G in which casein was replaced with gluten was used as a basal diet to avoid possible iodine contamination. In Experiment 1, F-344 rats of both sexes were sc injected with DHPN at a dose of 2800 mg/kg body weight and then fed a diet containing 0%, 0.8%, 4%, or 20% defatted soybean for 12 weeks, with proportional replacement of gluten by soybean flour. Although no thyroid proliferative lesions were found in any group, the absolute thyroid weights were significantly (p < 0.01) elevated with the 20% soybean treatment. In Experiment 2, after similar sc injection of DHPN, rats were fed a basal diet or a diet containing 20% soybean under iodine normal or deficient conditions for 12 weeks. Soybean feeding to both sexes under iodine deficient but not normal conditions dramatically enhanced the development of thyroid follicular adenomas (p < 0.01) and adenocarcinomas (p < 0.05), in good agreement with decrease in thyroxine and increase in thyroid-stimulating hormone. Thus co-exposure to excess soybean and iodine deficiency results in synergistic promotion of DHPN-initiated thyroid tumorigenesis in rats, of which mechanisms appear to primarily involve effects on serum hormone levels."
Specificity of co-promoting effects of caffeine on thyroid carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine.Son HY, Nishikawa A, Okazaki K, Kitamura Y, Kanki K, Lee KY, Umemura T, Hirose M. Toxicol Pathol. 2004 May-Jun;32(3):338-44.
"The specificity of
copromotion effects of caffeine with known goitrogenic factors on
thyroid carcinogenesis was examined in rats pretreated with
N-bis(2-hydroxypropyl)nitrosamine (DHPN). Male F344 rats were divided
into 8 groups, each consisting of 10 animals, and received a single sc
injection of 2,800 mg/kg DHPN. From one week after the DHPN
initiation, they were given basal diet, iodine deficiency (ID) diet,
500 ppm phenobarbital (PB) solution or 1,000 ppm sulfadimethoxine (SDM)
solution with or without 1,500 ppm caffeine feeding for 12 weeks. The
caffeine, PB, SDM, and ID treatments significantly (p < 0.05 or 0.01)
increased the relative thyroid weights, and the increases with PB or
ID were further (p < 0.05 or 0.01) enhanced in combination with
caffeine. SDM drastically promoted thyroid carcinogenesis in
association with increased serum TSH levels regardless of the caffeine
treatment. Thyroid follicular carcinomas and adenomas were more
frequently observed in the additional caffeine groups than in the ID
alone groups. The incidence and multiplicity of focal thyroid
follicular hyperplasias in the ID-treated groups were significantly (p
< 0.05 and 0.01) elevated in the case of combination with caffeine.
Increases in serum TSH levels with PB or ID were also further enhanced
in combination with caffeine. Serum thyroid hormone levels were
significantly (p < 0.01) decreased by SDM but significantly (p < 0.05
or 0.01) increased by caffeine, PB or ID. Our results clearly indicate
that dietary caffeine at a high dose of 1,500 ppm interacts with ID,
but neither SDM nor PB, to promote rat thyroid carcinogenesis although
the combined caffeine + PB treatment somewhat affected thyroid weights
as well as thyroid hormone levels."
Synergistic interaction between excess caffeine and deficient iodine on the promotion of thyroid carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine.Son HY, Nishikawa A, Kanki K, Okazaki K, Kitamura Y, Lee KY, Umemura T, Hirose M. Cancer Sci. 2003 Apr;94(4):334-7. [abstract only]
"The combined effects of caffeine (1,3,7-trimethylxanthine) with iodine deficiency (ID) were examined in a rat two-stage thyroid carcinogenesis model using N-bis(2-hydroxypropyl)nitrosamine (DHPN). Male F344 rats were divided into 6 groups each consisting of 10 animals, and received a single s.c. injection of 2800 mg/kg DHPN. From 1 week after the DHPN initiation, the rats were respectively fed a basal diet in which the protein was exchanged for 20% gluten, containing 1500 ppm caffeine + ID, 300 ppm caffeine + ID, 60 ppm caffeine + ID, 1500 ppm caffeine or ID or a basal diet alone for 12 weeks. Relative thyroid weights were significantly (P < 0.05) increased due to the development of proliferative lesions induced by the ID diet as compared to the DHPN-alone group value, which was enhanced by caffeine, albeit without statistical significance. Relative pituitary weights were significantly (P < 0.05) increased with 300 or 1500 ppm caffeine + ID as compared to the DHPN-alone group value. Serum thyroid stimulating hormone (TSH) levels were slightly increased by ID, an effect which was further enhanced by 300 or 1500 ppm caffeine. Serum thyroxine (T(4)) levels were slightly increased by caffeine or ID alone, but decreased by caffeine with ID. Histopathologically, thyroid follicular carcinomas were found only in the 1500 ppm caffeine + ID group, although thyroid follicular adenomas were detected in all the ID-treated groups. The multiplicity of focal thyroid follicular hyperplasias was significantly (P < 0.05) increased by 1500 ppm caffeine. These results indicate that caffeine may synergistically promote thyroid carcinogenesis with ID partially through a pituitary-dependent pathway in rats, implying the possible implication of routine caffeine intake in the promotion of thyroid carcinogenesis."
Synergistic effects of high-dose soybean intake with iodine deficiency, but not sulfadimethoxine or phenobarbital, on rat thyroid proliferation.Ikeda T, Nishikawa A, Son HY, Nakamura H, Miyauchi M, Imazawa T, Kimura S, Hirose M. Jpn J Cancer Res. 2001 Apr;92(4):390-5. [abstract only]
"The specificity and dose dependence of the synergistic effects of soybean intake with iodine deficiency on the induction of thyroid proliferation were investigated in female F344 rats. In the first experiment, rats were divided into 6 groups, each consisting of 5 animals, and fed a basal diet containing 20% gluten, an iodine-deficient basal diet alone or an iodine-deficient diet containing 0.2%, 1.0%, 5.0% or 25% defatted soybean for 5 weeks. Soybean feeding synergistically induced thyroid hyperplasias with iodine deficiency only at the 25% dose. In the second experiment, rats were also divided into 6 groups, each consisting of 5 animals, and fed a basal diet, a diet containing 20% defatted soybean, 0.025% sulfadimethoxine (SDM), 20% defatted soybean + 0.025% SDM, 0.05% phenobarbital (PB) or 20% defatted soybean + 0.05% PB for 5 weeks. The SDM treatments significantly (P < 0.05 - 0.01) increased the thyroid weights, but this increase rate was less prominent in the SDM + soybean group than in the SDM alone group. The PB treatment was also associated with a tendency for increase in thyroid weight, but again this was smaller in the PB + soybean group than in the PB alone group. Although the SDM or PB treatments reduced the serum triiodothyronine and thyroxine levels and consequently increased the serum thyroid-stimulating hormone (TSH) levels, the soybean feeding did not affect or rather attenuated these changes. Our results clearly indicate that soybean feeding does not synergistically enhance the effects of SDM or PB on the rat thyroid. Thus it can be concluded that soybean intake specifically interacts with iodine deficiency in induction of thyroid proliferative lesions in rats, only at high doses."
Lack of effect of soy isoflavone on thyroid hyperplasia in rats receiving an iodine-deficient diet.Son HY, Nishikawa A, Ikeda T, Imazawa T, Kimura S, Hirose M. Jpn J Cancer Res. 2001 Feb;92(2):103-8. [abstract only]
"We have reported a dramatic synergism between
soy intake and iodine deficiency regarding induction of thyroid
hyperplasia in rats. Because isoflavones are active constituents of
soybeans, in the present study, their possible contribution was
examined. Female F344 rats were divided into 8 groups, exposed to diet
containing a 0.2% soy isoflavone mixture (SI), 0.2% SI + iodine
deficiency (ID), 0.04% SI, 0.04% SI + ID, 20% defatted soybean (DS)
alone, 20% DS + ID, ID alone or basal diet alone for 5 weeks. Thyroid
weight was not influenced by SI, but was increased by the ID and DS
diets with a further significant increment in the DS + ID group (P <
0.01). Compared to the control value, serum T(4) was significantly (P
< 0.01) increased by 20% DS alone and decreased in all groups given
the ID treatment (P < 0.001). Serum thyroid stimulating hormone (TSH)
level was increased by ID, and further enhanced by DS (P < 0.01) but
not SI. Histopathologically, diffuse hypertrophy and / or hyperplasia
of thyroid follicles were observed in the ID-treated groups, the
severity being enhanced by DS but not SI. Proliferating cell nuclear
antigen labeling indices (%) were elevated in the ID diet groups and
again enhanced by DS, but not SI. These results thus suggest that
isoflavones may not be involved in the mechanisms underlying the
synergistic goitrogenic effect of soybean with iodine deficiency." |
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