Environmental and Molecular Mutagenesis - Legacy Tobacco ...

44 1989 EMS Abstracts
Notes major DNA adducts formed In an estuarine fish, C. varlgQAtus. as the result of exposure to
radioiabeled i14CJ cyclophosphamide . Mature females were allowed to swim In tx10-3M CP
for 5d then placed In tanks of clean water along with a mature male . The female was allowed
to depurate for a total of 5d then sacrificed and analyzed for radioactivity(body w/o ovaries
and ovarian tissue) by counting on a Packard TRI-CARB 1500 iiquid scintillation counter . All
eggs spawned during this period were collected and assayed for radioactivity . A subsample
of the eggs collected were subjected to cetyltrimethylammonlum bromide for the Isolation of
DNA (Murry and Thompson, 1980) and the major adducts formed characterized by high
performance liquid chromatography (Benson and Garner, 1987) . Kinetic data for the uptake
into adults and transfer of cyclophosphamide to eggs will be presented and contrasted to the
kinetics of uptake of CP in eggs directly from aqueous media . Data on the molecular binding
of cyclophosphamide to cellular DNA and chromosome aberration frequencies will also be
presented .
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
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COMBINED jjj VIVO DNA BINDING AND TUMOR DOSE-RESPONSE STUDIES TO INVESTIGATE THE
MOLECULAR DOSIMETRY CONCEPT . R . Dashwood, P . Loveland . A . Fong, J . Hendricks and
G . Bailey, Oregon State University, Corvallis, OR 97331 . (USA) .
Swenberg et al . (Prog .exp .Tumor Res .11 :42,1987) have discussed the possibility of
using " . the concentration of DNA adducts . . as a better exposure index for quantitative
risk assessment than . .the chemical's exposure concentration" . To evaluate this
molecular dosimetry concept, we have undertaken concomitant jD vivo DNA binding and
tumor dose response (d-r) studies in rainbow trout . In one approach, -10 000 animals
were exposed both to the carcinogen aflatoxin B1 (AFB1) in the dose-range 10-320 ppb
in diet, and to 5 doae levels of a natural anti-carcinogen known to reduce AFB1-DNA
binding in trout (indole-3-carbinol, I3C) . When each data-point from the 12 mo . tumor
d-r analyses was plotted with its corresponding AFB1-DNA binding data-point (logit %
tumor response vs (log) AFB1-DNA binding), a linear relationship was observed at each
13C dose-level . At I3C doses