There is increasing evidence that substances which are normally present in
human or animal bodies may, under the certain circumstances, exhibit
deleterious effects on genetic material, therefore acting as endogenous
mutagenic agents. Since hormones represent one of the best studied endogenous
mutagens, some research focused on the possible role of thyroid hormone in
mutagenesis and carcinogenesis. Indeed, thyroid hormones accelerate aerobic
metabolism and production of reactive oxygen species (ROS) and, therefore,
may exhibit mutagenic effects in various test systems on mammalian cells.
However, possible mutagenic effects on prokaryotic DNA has not been
investigated so far. Hence, the aim of this research was to compare the
sensitivity of TA 100 Salmonella typhimurium with and without metabolic
activation with S9 fraction, and human lymphocytes to possible genotoxic
effects of triiodothyronine (T3). Therefore, we used the reverse mutation
assay on S. typhimurium (Ames test) and in vitro Comet assay in isolated
peripheral blood human lymphocytes. In both tests-systems a broad spectrum of
T3 concentrations was applied. The obtained results showed absence of
genotoxic effects of T3 in bacterial reverse mutation assay and very profound
genotoxic effects in human lymphocytes at concentrations higher than 15 ?M.
We only observed cytotoxic effects in bacterial system at very high T3
concentrations (300 and 500 ?M). In conclusion, T3 was unable to increase the
level of reverse mutations in Ames test both with and without S9 mix.
Therefore, it seems that ROS production in mitochondria may be the primary
cause of DNA damage caused by T3 in mammalian cells.
Genotoxic Effects Induced by Fotemustine and Vinorelbine in Human Lymphocytes
