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NATIONAL CENTER FOR ATMOSPHERIC RESEARCH

P. O. Box 1470 ¢ Boulder, Colorado 80302
Telephone: {303} 494-515] @ TWX: 910-940-3245 @ Telex: 45694

2 January 1975

Professor Joshua Lederberg

Department of Genetics

Stanford University School of Medicine
Stanford, California 94305

Dear Professor Lederberg:

I would greatly appreciate your advice on two important questions
regarding radiation induced mutations and cancer in man:

(1) What is the published evidence that would support the view that
natural radioactivity cannot account for observed rates of
mutation in living cells? In connection with an early suggestion
by Hermann Muller (Amer. Nat. 64, 220, 1930) to the effect that
the high spontaneous mutation rate in Drosophila could not be
explained on the basis of natural radiation, I would point out
that the Brownian motion of the very small airborne dust particles,
to which the short-lived radioactive daughters of radon-222 are
attached, may result in substantial alpha activity accumulation
on Drosophila as well as on other airborne insects, bacteria and
viruses. On this basis, the cumulative alpha radiation dose,
principally that from 214d, may explain the observed high
incidence of spontaneous mutation. I also note that seedling
plants, grown from seeds stored for various periods of time,
reportedly exhibit an incidence of mutations which increases
with increased time of seed storage. In this case, it is
conceivable that the accumulation of *!°Pb on the seed coverings
during plant growth, the subsequent ingrowth of 210bo, and the
cumulative 7}°%Po alpha dose to the stored seed may explain the
observations. Thus, for these two cases the processes may be
analogous to those involved in the accumulation of 210p_ and 7} °Po
on tobacco trichomes and insoluble cigarette smoke particles,
described in the enclosed reprint. Is there any convincing evidence
of spontaneous mutations not attributable to radiation? Can you
please give me the references to the most recent published discussions
of the adequacy of radiation as the agent of spontaneous mutations
in nature.

(2) My second question concerns the availability of published evidence
on the nature of the somatic cell mutations which give rise to
malignant cells in mammals and man. Do they involve gene mutations
alone, chromosome structural changes, or a combination of the two?

The National Center for Atmospheric Research is Operated by the University Corporation
for Atmospheric Research under sponsorship of the National Science Foundation.
Professor Joshua Lederberg
2 January 1975
Page 2

If one or more multiple breaks in the chromosomes of the original
normal cells are essential to give rise to the structure of the
product malignant cell, then it would follow that internal alpha
emitters would play a very important role in the incidence of
human cancer. This appears to me to be a key question relevant
to assessing the relative importance of chemicals, viruses and
radiation as agents of human cancer.

I would value your comments on these questions and would appreciate
references to recent published discussions of them. May I also have reprints
of your own recent articles bearing on these problems. Thank you.

Sincerely yours,
Sia dli|ilcbar
Edward A. Martell

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