point, all of the animals were exposed to the same amount of
aflatoxin. But what if the initial aflatoxin exposure is varied? Would protein
55
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CHART 3.4: DIETARY PROTEIN AND FOCI FORMATION
3.5
3.0
2.5
OJ
2.0
VI
c
0
0..
VI
1.5
OJ
0:::
'0
0
1.0
l.L
.5
0
20%
5%
Dietary Protein Level
CHART 3.S: CARCINOGEN DOSE VERSUS PROTEIN INTAKE
100 /
./
90
80
70
OJ
VI
c
60
0
0..
VI
50
OJ
0:::
'0
40
0
l.L
30
20
.....
10
...
./
~
1
0 1.1
LowAF
High AF
High Protein
Low Protein
THE (HINA STUDY
56
still have an effect? We investigated this question by giving two groups
of rats either a high-aflatoxin dose or a low-aflatoxin dose, along with a
standard baseline diet. Because of this the two groups of rats were starting
the cancer process with different amounts of initiated, cancerous "seeds."
Then, during the promotion phase, we fed a low-protein diet to the high-
aflatoxin dose groups and a high-protein diet to the low-aflatoxin dose
group. We wondered whether the animals that start with lots of cancerous
seeds are able to overcome their predicament by eating a low-protein diet.
Again, the results were remarkable (Chart 3.5). Animals starting with
the most cancer initiation (high-aflatoxin dose) developed substantially
less foci when fed the 5% protein diet. In contrast, animals initiated with
a low-aflatoxin dose actually produced substantially more foci when sub-
s e q u e n t l y fed the 20% protein diet.
A principle was being established. Foci development, initially deter-
m i n e d by the amount of the carcinogen exposure, is actually controlled
far more by dietary protein consumed during promotion. Protein dur-
ing promotion trumps the carcinogen, regardless of initial exposure.
With this background information we deSigned a much more sub-
stantial experiment. Here is a step-by-step sequence of experiments,
carried out by my graduate student Linda Youngman.35 All animals were
dosed with the same amount of carcinogen, then alternately fed either
5% or 20% dietary protein during the twelve-week promotion stage.
We divided this twelve-week promotion stage into four periods of three
weeks each. Period 1 represents weeks one to three, period 2 represents
weeks four to six, and so on.
When animals were fed the 20% protein diet during periods 1 and 2
(20-20), foci continued to enlarge, as expected. But when animals were
switched to the low-protein diet at the beginning of period 3 (20-20-
5) , there was a sharp decrease in foci development. And, when animals
were subsequently switched back to the 20% protein diet during period
4 (20-20-5-20), foci development was turned on once again.
In another experiment, in animals fed 20% dietary protein during
period 1 but switched to 5% dietary protein during period 2 (20-5), foci
development was sharply decreased. But when these animals were re-
t u r n e d to 20% dietary protein during period 3 (20-5-20), we again saw
the dramatic power of dietary protein to promote foci development.
These several experiments, taken together, were quite profound. Foci
growth could be reversed, up and down, by switching the amount of
protein being consumed, and at all stages of foci development.
57
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These experiments also demonstrated that the body could "remem-
b e r " early carcinogen insults,35, 36 even though they might then lie
dormant with low protein intake. That is, exposure to aflatoxin left a
genetic "imprint" that remained dormant with 5% dietary protein until
nine weeks later when this imprint reawakened to form foci with 20%
dietary protein. In simple terms, the body holds a grudge. It suggests
that if we are exposed in the past to a carcinogen that initiates a bit of
cancer that remains dormant, this cancer can still be "reawakened" by
bad nutrition some time later.
These studies showed that cancer development is modified by relative-
ly modest changes in
radhika.iyer
The Knight of Rosecliffe
Elaine Viets
David Achord
Brian Ruckley
Rachael Wade
Niki Burnham
Susan May Warren
Sydney Bristow
Lee Harris