From: fulk@cs.rochester.edu (Mark Fulk)
Newsgroups: sci.bio,sci.chem,sci.med
Subject: Re: Carcinogens
Date: 29 Sep 92 15:15:53 GMT
Organization: Computer Science Department University of Rochester

In article <dl10697.717637409@ehsn3.cen.uiuc.edu> dl10697@ehsn3.cen.uiuc.edu (Duc Trieu Le) writes:
>
>hi Everyone,
>
>I have just read in a book that lists Progesterone, Testosterone,
>Estrogens, and Androgens as being carcinogenis substances. I was
>under the assumption that our bodies have certain amount of these
>sex hormones. I was wondering why these hormones are carcinogenic
>and what effects do they have on our bodies if excess amounts are
>detected. thanks in advance.
>
>--
>Duc T. Le
>led@sunfs1.dsd.northrop.com

I'll try to keep this short and unpedantic :-)

The currently accepted theory of carcinogenesis offers some useful
distinctions here.  Substances which formerly might all have been
called carcinogens are now divided into (at least) three categories:

Primary carcinogens:

These cause the somatic mutations which are the proximal cause of cancer.
They may act directly or indirectly; most often, they act indirectly.
The classic example is benzo-a-pyrene (bap), a potent carcinogen in
cigarette smoke.  bap is metabolized to something else, which binds to
DNA.  The DNA repair enzymes in the cell misread the bound DNA as
containing a mistake, and ``repair'' it, leading to a mutation.  If
the mutation occurs in one of the forty or so cellular oncogenes,
one step in the development of cancer may have occurred.

Immune system suppressors:

The immune system includes a subsystem, comprised partly of the ``natural
killer'' T-cells, that suppresses nascent cancers.  There are a variety
of substances and conditions that suppress the natural killer T-cells;
one such condition is AIDS, another, more controversial, example is
clinical depression.

Promoters:

This is where your hormones come in.  There are a variety of substances
and conditions that, in general, encourage cell growth.  For many hormones,
cell growth promotion is part of the function of the hormone; thus,
luteinizing hormone encourages the growth of follicular cells in the
ovary.  These substances become cancer promoters when there is a cell,
already partly along the pathway to becoming a cancer cell, whose growth
is promoted by the substance.

The primary mutation of a precancer cell will generally cause it to
either be more sensitive to growth promoters, or less sensitive to
cell growth inhibitors.  The classic example is rsc, the oncogene
found in the Rous sarcoma virus: this mutation causes a cell to break
down the adhesion plates that bind it to nearby cells; contact with
other cells is an important inhibitor of mitosis.  A cell with an rsc
mutation will not do much, in general, but stimulate it with some
platelet-derived growth factor (PDGF), for example, and it will divide
while its neighbors, inhibited by their adhesion plates, don't.  The
end result of the mutation plus a period of promotion is the formation
of a clone of rsc-mutated cells; this clone may even be large enough to
be called a bulk tumor.

Now the existence of this clone greatly increases the probability that
one rsc-mutated cell will pick up another mutation (perhaps sis, that
causes the cell to make its own PDGF) along a path to cancer.

Conclusion:

The sex hormones that you listed are all part of a complex system of
interacting hormones that controls, among other things, sex organ
formation, ovulation, the number of ova released per cycle, and general
bodily form.  Luteinizing hormone, that I mentioned above as encouraging
cell growth in ovarian follicles, is also part of that system.

Given the complexity of this system of hormones, I would expect that
a given hormone could have a net effect of promoting one sort of
cancer, and inhibiting another.  These effects are likely to be modulated,
even reversed, by other conditions in the patient, including weight,
gender, age, other medical conditions, and medications.

Although I don't think the final answers are in, it appears that
estrogen treatments of women tend to increase the (rather low)
probability of ovarian cancer while decreasing the (much higher)
probability of breast cancer.

Postscript:

I believe that the distinctions made above are now well-established
enough that we should start basing public policy on them.  For example,
the Anderson amendment should be revised in accord with new understanding.
The outright ban on carcinogens should be restated with a threshold on
mutagenic activity, and it should be recognized that promoters may be
active in some animals but not in humans, as well as vice-versa.  (Primary
carcinogens are mostly pretty universal.)  We will need to recognize that
a powerful promoter should be regulated more strongly than a weak primary
carcinogen.  One thing that is necessary for this to happen is that
the public be educated about our new understanding of cancer.  The last
fifteen years have indeed been revolutionary in cancer research, and we
should start reaping the benefits soon.

References:

For the modern theory of cancer, look up review articles in Nature.

I learned what I know about the system of sex hormones from Mike
Lacker at NYU; his ca. 1979 thesis at the Courant Institute of Math.
is an examination of the control of ovulation number by the interaction
of estrogen and luteinizing hormone; he also gained some understanding
of amenorhea and the multiple-birth effects of fertility drugs.  I don't
know where he is now.
-- 
Mark A. Fulk			University of Rochester
Computer Science Department	fulk@cs.rochester.edu