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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 />

398<br />

399<br />

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 />

400

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