Project Title:
13,
Biological Studies of Materials Arising from Energy Operations
Free Radical Studies on Mechanisms of Action
of Pollutants
Project not yet
14,
RX-03-06- (a)
Publications:
initiated,
Scope:
A)
200 Word Summary:
This proposal includes two major investigative projects:
free radical
studies of pollutant carcinogens and mutagens, and free radical studies of
ozone and nitrogen oxide and of nitrate toxicity,
Recently, evidence has
been forthcoming that some chemical carcinogens act by combining with DNA
by way of free radical reactions, These carcinogens include many of the
atmospheric pollurants produced by the burning of fossil fuels for both
electrical and automotive power (such as polycyclic hydrocarbons), and there
are indications that some secondary products of pollution that are’ components
of photochemical smogs (such as ozone and higher nitrogen oxides) may also
be carcinogenic in a similar way,
The immediately reactive ("proximate")
forms of the carcinogens, following conversion by cellular metabolism,
appear to be cationic free radicals or possible chemically related epoxides,
The special EPR facilities developed at BNL are uniquely suited to monitor
reactions of this kind, whose analysis should contribute significantly to
a systematic understanding of those molecular properties of pollutants which
lead to carcinogenesis or to mutagenesis (which appears to be a closely
related process at the cellular level).
A free radical test system monitored -
by EPR holds promise as a rapid, presumptive screening test for carcinogenicity
among a group of hydrocarbons,
B)
Supplement to 200 Word Summary:
-
The ongoing research at BNL (see RX-03-02-c) could readily be extended
to include relevant pollutants, The responses of reactions involving radicals
produced from pollutants in the presence of DNA constituents to different free
radical generating systems (physical, chemical, and enzymatic) and to the
inhibiting (protective) effects of antioxidants, free radical scavengers,
etc., would be followed by EPR methods, which would also be assessed
their possible ucility in assaying pollutant toxicity.
for
However, the value
of these free radical studies in evaluating the carcinogenic and mutagenic
potential of pollutants could be amplified by coordinated investigations of
three kinds: 1) biophysical measurements of the complexed product of
carciapgen/mutagen attached to DNA or to its constituents, 2) kinetic
analyse of the free radical combining reactions, and 3) evaluations of
al factors that could relate the reactions being studied more
to possible toxicity in vivo.
These related studies are discussed
further:
1)
Nuclear magnetic resonance (NMR) spectroscopy can be used to help
Although
of the attachment of carcinogens to specific sites.
details
reveal
(See Continuation Sheet)
1119323
RX=- 380