Toxicology of Industrial Compounds

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Figure 19.5 Factors influencing the development of thyroid neoplasia.
Two consecutive processes are thought to occur in the development of
thyroid tumours; first, initiation which occurs quickly and is irreversible
and secondly, promotion which occurs slowly and is reversible (and for
which cell proliferation may be a necessary but not sufficient condition).
Initiators may be ionising radiation, chemical/biological agents or genetic
factors, with TSH acting as a promotion agent. Spontaneous thyroid
follicular cell tumours arise from unknown aetiologies and factors and ageinduced
changes in the cell membrane, growth factor and signaltransduction
mechanisms may be involved. Small subpopulations of hyperreactive
epithelial cells retaining the high replication rate of the foetal stage
have been identified (Peter et al., 1982; Smeds et al., 1987) which may
enter clonal expansion following only slight elevations in TSH (such as
those in handled or stressed animals) or other growth factors, leading to
spontaneous nodular goitres (see Zbinden, 1987).
Many experimental studies have confirmed the key role of TSH as a
stimulator of thyroid growth. In a rat thyroid cell line (FRTL-5) TSHstimulated
growth of the cells was found to be associated with a marked
increase in c-fos and c-myc oncogene expression (Colletta et al., 1986).
Another example of the tumour promoting capacity of TSH is given by