Project Title:

13.

Biclogical Studies of Materials Arising

from Energy Operations

Interaction of Chemicals with Nucleic Acids

Publications:

RX-93-06-(b)

Project not yet initiated.
~4,

Scope:
A)
200 Word Summary

One of the long-range effects of non-nuclear energy systems urgently
needing analysis is carcinogenesis (oncogenesis).
This involves more than
the direct effect in present generations since there is the possibility of

genetic damage,
Chemical carcinogens given at low doses over long periods
of time present the same problem as do low doses of radiation at low dose
rates:
one has to extrapolate experience from high to low doses,
Since
the hazard from low doses of common pollutants generated by non-nuclear
energy sources would only be deducible from a precise understanding of how
these pollutants induce effects, studies are needed on how such environmental contaminants interact with the informational macromolecules, that
ts to say, nucleic acids,
This approach offers the opportunity not only
of understanding how toxic chemicals induce biological damage, but may
also indicate ways to minimize damage.
As knowledge of these interactions
increases, it may serve as a rapid detection system for chemicals likely
to cause genetic damage and tumors,
The aim of this study is prediction, not description--to tell before

the fact what kinds of molecule are likely to cause intense pharmacological
effects, notably oncogenesis and genetic effects.
B)

Supplement

to 200 Word

Summary:

A survey will be made of soluble carcinogens (soluble in physiological

solution) apart from polynuclear hydrocarbons--emitted from fossil-fuel
power generating plants, and of soluble carcinogens--apart from polynuclear

heterocyclic compounds and polynuclear aromatic hydrocarbons--present
in urban atmosphere,

Chemicals recognized as directly carcinogenic will

be complexed with DNA, double-stranded RNA, and synthetic RNA so as to
detect their exact points of interaction,
The interaction of the carcinogens
in highly specific ways with the DNA and RNA will be followed spectrophoto-

metrically, by melting-curve analyses, and, when indicated by ultracentrifugation analyses.
Im critical cases, x-ray diffraction studies will be made of
fibemm. of complexes and the data from these combined with molecular modelbui
® to provide rigorous proof on the stereochemistry of the interaction
of
¢hemical with the nucleic acid,
15,

Relationship to Other Projects:

The proposed program extends to environmental pollutant studies on the

interaction of drugs with nucleic acids carried out under budget activity

(See Continuation Sheet)

11193249

RX - 386

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