Environmental and Molecular Mutagenesis - Legacy Tobacco ...
Environmental and Molecular Mutagenesis - Legacy Tobacco ...
Environmental and Molecular Mutagenesis - Legacy Tobacco ...
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138 1989 EMS Abstracts<br />
Notes ETHICS AND THE ALLOCATION OF RISK : SCIENCE AND VALUES<br />
Thomas H. Murray, Ph .D .<br />
Center for Biomedical Ethics<br />
School of Nedicine<br />
Case Western Reserve University<br />
Clevel<strong>and</strong> OH 44106<br />
http://legacy.library.ucsf.edu/tid/clb93d00/pdf<br />
A large number of ethical questions posed by research on<br />
environmental mutagenesis need to be sorted out. They include<br />
research on human subjects, the responsible use of information,<br />
privacy <strong>and</strong> others . This paper will focus on an ethical question<br />
with considerable social importance : How should scientific findings<br />
<strong>and</strong> moral values be used in making public policy decisions about<br />
the control of mutagenic substances in the environment <strong>and</strong> in the<br />
workplace? The values that guide judgments about the relative<br />
certainty of scientific claims differ from the st<strong>and</strong>ards that are<br />
<strong>and</strong> should be used in making public policies that ought to be<br />
informed by scientific findings. The struggle over regulation of<br />
asbestos will form a case study of the interplay between science<br />
<strong>and</strong> values in the making of public policy on toxic substances .<br />
Such social decisions pose unavoidable questions about the<br />
allocation of risk, which are also ethical questions, specifically<br />
questions about justice .<br />
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APPLICATION OF THE 32P-TECHNIQUL+ TO DETECT DNA-ADDUCTS BY CISPLATI N<br />
R . Mustonen <strong>and</strong> K . Hemminki . Institute of Occupational Health .<br />
Helsinki . Finl<strong>and</strong><br />
The main reaction products of Sjg-diamminedichloroplatinum (II),<br />
cisplatin. with DNA are intrastr<strong>and</strong> cross-links with dGpdG <strong>and</strong> . to a<br />
lesser extent, dApdG . Platinum can be conveniently measured by atomic<br />
absorption spectroscopy but with patient white blood cell DNA this<br />
technique is presently at the limit of its sensitivity . We have<br />
therefore applied the 32P-postlabelling technique to the DNA adducts<br />
of cisplatin . The st<strong>and</strong>ard compound, intramolecular crosslink Pt-dGpdG<br />
is labelled with T4 polynucleotide kinase <strong>and</strong> Y-32P-ATP, <strong>and</strong> the<br />
products are separated by PEI-TLC <strong>and</strong> visualized by autoradiography .<br />
st<strong>and</strong>ards containing a 5'-phosphate group are used as internal<br />
st<strong>and</strong>ards . The phosphorylation of the cisplatin-adducts is a slow<br />
process as compared to that of polycyclic adducts . but the levels of<br />
adducts detected with the st<strong>and</strong>ard compounds are presently belo w<br />
100 fmol . Adducts are also detected in DNA platinated vitro <strong>and</strong><br />
digested enzymatically to nucledtides .<br />
CATECHIN AS AN ANTIMUTAGEN AND ANTICARCINOGEN .<br />
M. Nagabhushan, Northwestern Universit , Department of Pathology, 303<br />
E. Chicago Ave., Chicago, IL 60611, U~A .<br />
Betelquid chewing with or without tobacco is correlated with high incidence of oral<br />
cancer in India. Betelquconsists of betelnut, betelleaf, catechu, slaked lime <strong>and</strong> spices .<br />
Catechu is a nonawtagenic constituent of betelquid contain catechin as the principal<br />
compound. Catechu extract <strong>and</strong> catechin inhibits the muugeniciry of tobacco, masheri, bidi<br />
<strong>and</strong> cigarette smoke condensates, smoked meat charred <strong>and</strong> noncharred extracts, benzo(a)<br />
pyrene (BP) <strong>and</strong> dimethylbenz(a) anthracene (DMBA) in a dose dependent manner in<br />
salmonella/microsome test. Catechin inhibits the activity of Cyt P 450 <strong>and</strong> has no effect<br />
on GST, but increased (1SH content in rat liver. Simultaneous treatment of catechin<br />
prevents the mutagenicity of BP <strong>and</strong> DMBA metabolitis but pre or post-tteatment of<br />
bacteria with catechin has no effect on the mutagenicity. Catechin also inhibited the in vitro<br />
binding of 3HBP metabolitis to calf thymus DNA . Oral administration of catechin inhibits<br />
the incidence of BP-induced forestomach tumors in female swiss mice . This study<br />
indicates that catechu in betelquid may act as an antimutagen <strong>and</strong> anHcarcinogen <strong>and</strong> may<br />
suppress the mutageniclcarcinogenic potential of other betelquid ingnedients .<br />
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