A group of scientists used rats as specimens for an experiment designed to test the transformation of cells. Transformation is a cell process in which normal cells become cancerous. (Experiment modified from lecture material, WSU, College of Science, Dr. John Taylor, Cancer Cell Biology)
The scientists used two kinds of chemicals in their experiments to test rat cell transformation. The chemicals belonged to two groups--an initiation group (I) and a promotion group (P).

The chemicals were pasted to the back (or dorsal) surface of the rats' chest cavities on day one with no further applications of the chemical. After the time period of five years, cells from the patch where chemicals were pasted, were viewed and analyzed under the microscope. Cells that did NOT
transform were labeled (NC) for normal cells. Cells that did transform were labeled (CC) for cancerous cells. Groups of 100 rats were tested in each of the following experiments. Many series of experiments were begun on the same day and data collection on transformation began at the end of five years. (Some exceptions are noted in the following details of each trial.)

Series One
One rat group had only the
(I) pasted to their backs on day one. Another group, had only the (P) pasted to their backs on day one. After five years, the cells from each group of rats were analyzed for transformation. None of these cells from either group were transformed, so all were labeled (NC) for normal cells.
What might these data from series one tell us about these chemicals and transformation?

Series Two
In the next series of experiments, one rat group had the
(I) pasted to their backs on day one and again on day 30. Likewise, another rat group had the (P) pasted to their backs on day one and again on day 30. After five years, the cells from each rat group were analyzed for transformation. None of these cells from either group were transformed, so all were labeled (NC).
What might these data from series two tell us about these chemicals and transformation?

Series Three
In one group of rats, the
(I) chemical was pasted on day one and the (P) chemical was pasted on day 30. After five years, these cells were analyzed for transformation. ALL cells had transformed and were labeled (CC) for cancerous cells. The next rat group was tested by pasting the (P) chemical to their backs on day one and the (I) chemical to their backs on day 30. After five years, these cells were analyzed for transformation and all were normal (NC).
What might these data from series three tell us about these chemicals and transformation?

Series Four
In this next series of tests, scientists exposed one rat group to the
(P) chemical on day one, the (I) chemical on day 30, and the (P) chemical on day 60. After five years, these cells were analyzed for transformation. ALL cells were cancerous and labeled (CC). In the final rat group to be tested, the (I) chemical was pasted on day one and the (P) chemical was pasted two years later. After five years, the cells were analyzed. ALL cells were cancerous and labeled (CC).
What might these data from series four tell us about these chemicals and transformation?


How could you summarize these experimental data and apply it to human cell transformation?














Series One Data might be interpreted in the following way...
One application of either the (I) or the (P) chemical will NOT lead to cancer in rats.
















Series Two Data might be interpreted in the following way...
Two applications of (I) will not lead to cancer in rat cells. Two applications of (P) will not lead to cancer in rat cells.














Series Three Data might be interpreted in the following way...
The order in which (I) and (P) are applied to the rats determines the presence or absence of cancer. If (I) chemical is applied before (P), then cells in rats become cancerous. If (P) is applied before (I), then rat cells remain normal.













Series Four Data might be interpreted in the following way...
Cancer occurs only if (P) follows (I) exposure. And the amount of time that exists between chemical exposures is not relevant. What matters is, if (P) exposure follows (I) exposure even up to two years, cancer will develop in rat cells.

















Summarize these experimental data
Exposure to chemicals contributes to transforming normal cells into cancer cells. However, the kind of chemical exposure, whether an initiator (I) or a promoter (P), and the sequence of the types of chemicals that a rat is exposed to determines the presence or absence of cancer cells. If the sequence of exposure is (I) before (P), it does not matter if the rat is exposed to (P) immediately after (I) is introduced or years later.What matters is, if (P) comes after (I) exposure, rats get cancer.


Since rats are vertbrate mammals, it follows that we might apply this information to human
transformation.

Is is possible that human cells need at least two exposures to two different kind of chemicals and in a specific sequence prior to some kinds of cancer formation???

What are these
(I) and (P) chemicals?

Does the manner in which one is exposed (inhaled, ingested, skin contact) to these chemicals impact
transformation?