The various procedures in which radioactive isotopes play a major role
have been applied to many studies and investigations in the fields of
biology and medicine. In fact, most of the concepts of modern biology
that we have been discussing in this booklet owe their discovery to the
judicious use of radioisotopes. To illustrate how radioisotopes can be
used to solve a practical problem, we have chosen a typical example, the
investigation, at a molecular level, of the effectiveness of an
anti-cancer drug.
Several drugs that exert a beneficial effect, at least temporarily, on
the course of certain cancers have been used by doctors for several
years. Most of them were discovered empirically, that is, by accident,
during routine trials against cancers. Doctors know they work but do not
always know how. They would also like to know the mechanism of the
drugs’ action at the molecular level so that the knowledge might open
the way to the discovery of other drugs more effective against cancer
and less toxic against normal cells. The following experiment shows how
the molecular effect of an anti-cancer drug is studied.
[Illustration: Figure 28 _Technician preparing tissues for comparative
studies._]
Cells growing in tissue cultures are often used to test anti-cancer
drugs (see Figure 28). These cells, derived from human cell lines, are
grown in glass or plastic bottles as a suspension in a nutrient medium.
To begin, a culture is divided into halves. To one half is added the
anti-cancer drug Actinomycin D. The other half will continue to grow
without addition of other substances and will serve as a control, or
comparison. After a suitable time has elapsed for the drug to act on the
cultured cells, similar portions of the drug-treated cells and the
control cells will be tested in several ways. One portion of each kind
of cells is incubated with ³H-thymidine to determine the effect of the
drug on DNA synthesis. Two other portions are incubated with ³H-cytidine
to study the effect on RNA synthesis. Another pair will be tested with
¹⁴C-leucine to investigate protein synthesis. The effect of the drug, of
course, is determined by comparing the untreated control with the
drug-treated culture.
The biochemical, autoradiographic, and counting techniques that we
described previously are all used to determine the uptake of the
radioisotopes into the cell’s components. Chromatography is used to
ascertain if the drug has changed the concentration of precursors
(thymidine, cytidine, or leucine) in the nutrient medium, since a change
in these could produce misleading results. Finally, if the drug is found
to have an effect on RNA, we can investigate the type of RNA that is
affected by centrifuging phenol-purified RNA.
The results will disclose the primary site (DNA, RNA, or proteins) of
the drug action on cell metabolism. More elaborate experiments can
pinpoint more intimately the mechanism of action. By studying the life
processes of cells, we can advance toward a common denominator in
anti-cancer drugs that will lead to an effective anti-cancer treatment.