There is now a wealth of literature devoted to understanding the endocrinology of the
thyroid-pituitary axis and to describe in detail how the function of the thyroid gland can
be disrupted by various xenobiotics. The rat thyroid gland appears to be particularly
sensitive to adverse effects on these compounds and, inevitably, in long-term
oncogenicity studies, results in the development of thyroid follicular cell tumours. At this
time, ionizing radiation is the only acknowledged human thyroid carcinogen, a finding
well established in experimental systems also. Although humans respond to goitrogenic
stimuli as do animals, with the development of cellular hypertrophy, hyperplasia, and
sometimes nodular lesions, even in its moderate to severe form, it is not an established
aetiological factor for human thyroid cancer.
Because of marked species differences in thyroid gland physiology and apparent
susceptibility to hypothyroidism, the rodent is an inappropriate model for the
extrapolation of thyroid cancer risk to man for chemicals that operate secondary to
hormone imbalance. For such compounds the onus is on the investigator to demonstrate
this imbalance and to establish the cause and mechanisms of response. It is also essential to demonstrate that the compound is not genotoxic and has no effect other than through modifying thyroid homeostasis.
There is now a wealth of literature devoted to understanding the endocrinology of thethyroid-pituitary axis and to describe in detail how the function of the thyroid gland canbe disrupted by various xenobiotics. The rat thyroid gland appears to be particularlysensitive to adverse effects on these compounds and, inevitably, in long-termoncogenicity studies, results in the development of thyroid follicular cell tumours. At thistime, ionizing radiation is the only acknowledged human thyroid carcinogen, a findingwell established in experimental systems also. Although humans respond to goitrogenicstimuli as do animals, with the development of cellular hypertrophy, hyperplasia, andsometimes nodular lesions, even in its moderate to severe form, it is not an establishedaetiological factor for human thyroid cancer.Because of marked species differences in thyroid gland physiology and apparentsusceptibility to hypothyroidism, the rodent is an inappropriate model for theextrapolation of thyroid cancer risk to man for chemicals that operate secondary tohormone imbalance. For such compounds the onus is on the investigator to demonstratethis imbalance and to establish the cause and mechanisms of response. It is also essential to demonstrate that the compound is not genotoxic and has no effect other than through modifying thyroid homeostasis.
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