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Environmental and Molecular Mutagenesis - Legacy Tobacco ...

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136 1989 EMS Abstracts<br />

Notes based descriptors that focus on details of the molecular structures . The descriptors were analyzed<br />

statistically in order to develop a minimal set to characterize the compounds . Pattern recognition<br />

techniques were used to classify the compounds as active or inactive based on the structural<br />

descriptors. A training set of 80 compounds (40 active <strong>and</strong> 40 inactive) was classified almost perfectly<br />

using 15 descriptors, <strong>and</strong> the remaining compounds formed a prediction set of unknowns . Studies in<br />

progress are aimed at refining our SAR model for PAH mutagenicity .<br />

http://legacy.library.ucsf.edu/tid/clb93d00/pdf<br />

CLONING ILLID PARTIAL C11WCP6RIZATION OF RftE H(A7)1N IXCISION RLPAIR GENB ERCC-5 .<br />

J .S . Mudgett, G .F . Strniste, <strong>and</strong> ri .A. MacInnes, Genetics Group, LS-3, M886, Los<br />

A,lamos National Laboratory, Los Alamos, t39 87545 (iJSA) .<br />

The human excision repair gene DtCC-5 was identified <strong>and</strong> isolated by complementation<br />

of the W-sensitive Chiness hamster ovary cell mtutant UV-135 <strong>and</strong><br />

subsequent cosmid library construction <strong>and</strong> analysis . Genomic DtA from repair<br />

proficient human skin fibroblasts was ligated to pSV2gpt <strong>and</strong> transferred into<br />

W-sensitive Ctq cells of complementation group 5(W-135) . DNA from a primary<br />

MAX (aycophenolic acid, adenine, xanthine) resistant, W-resistant cell line was<br />

transferred into W-135 cells to isolate a secondary Mhe, W cell line, from<br />

which tertiary MaX`, i)V' cell lines were isolated by gene transfer . Cotuid<br />

clones which contained inserted human sequences wsre obtained from a 20X genumic<br />

library of the secondary transformant . None of thse individual (101) cosmid<br />

clones isolated <strong>and</strong> tested were able to ca .plement the repair defect, but<br />

specific overlapping pairs of cosmids co-transfected into UV-135 cells yielded<br />

transformnnts at high frequency which exhibited wild-type W resistance, suggestit~g<br />

that the repair gene is as large or greater than the cosmid insert size<br />

(-40 kb) . The overlap between the appropriate cosmid clones, <strong>and</strong> the coaplete<br />

contiguous human genomic insert, will be napped to identify the sise <strong>and</strong> functional<br />

boundaries of the human nNA repair gene . Unique huswt sequence probes<br />

derived from these specific cosmid clones were used to : 1) demonstrate a positive<br />

hybridization correlation with genomic tx4A from independent UV-resistant<br />

transformants <strong>and</strong> human cell hybrids ; 2) to confirm the previous assignment of<br />

ERCC-5 on chromosome 13 ; <strong>and</strong> 3) to screen c0Nuh libraries . (Supported by the<br />

U .S . Department of Snerqy under c^ntract W-7405-lN".-36)<br />

392<br />

393<br />

IN VIVO GENOTOXICITY OF TERTIARY BUTYL HYDROQUINONE IN GERM CELLS OP MALB<br />

NICE . A . Mukher,)ee <strong>and</strong> A . Sharma, Centre for Advanced Study in Cell <strong>and</strong> Chromosome<br />

Research, Department of Botany, University of Calcutta, 35 Ballygunge Circular Road,<br />

Calcutta 700 019 (INDIA)<br />

Effect of tertiary butyl hydroQuinone (doses of 10, 20 <strong>and</strong> 100 mg/kg/day during<br />

14 days) on germ cells of male mice were investigated . The mode of application was<br />

stomach intubation . The germ cell stages analysed were spermatids (for the heritable<br />

effects) <strong>and</strong> differentiating <strong>and</strong> stem-cell spermatogonia (for direct effects) . A lack<br />

of heritable translocations, sperm abnormalities was demonstrated in F males originating<br />

from treated P males . Significant effects in treated males were found with respect<br />

to . (1) sex-chromosomal univalency in the diakinesis-metaphase I stage after the<br />

treatment of stem spermatogonia, (2) sperm-head abnormalities after treatment of<br />

differentiating spermatogonia <strong>and</strong> (3) fertility after treatment of spermatids .<br />

394<br />

MICRONUCLEI INDUCED BY TERTIARY BUTYL HYDROQUINONE (AN ANTIOXIDANT) IN BONE MARROW<br />

CELLS OF MICE . Anita Mukherjee . Human Genetics Unit, Centre for Advanced Study<br />

in Cell <strong>and</strong> Chromosome Research, Department of Botany, University of Calcutta,<br />

35 Ballygunge Circular Road, Calcutta 700 019 . India .<br />

Tertiary butyl hydroquinone (TBHQ) a phenolic antioxidant was administered to<br />

Swiss albino male mice of 20, 50, 100 <strong>and</strong> 200 mg/kg as a single (i .p .) injection .<br />

Corn oil <strong>and</strong> cyclophosphamide were used as the vehicle (negative) <strong>and</strong> reference<br />

(positive) control respectively . Samples of bone marrow were examined for the<br />

incidence of micronuclei in the poiychromatie erythrocytes at 24 hours after dosing .<br />

A positive dose response effect in the micronuclei freQuency was observed following<br />

the Cochran Armitage Trend Test . 50, 100 <strong>and</strong> 200 mg/kg of TBHQ caused an increase<br />

in the incidence of micronuclei compared to the negative vehicle control . Cycl,ophoephamide<br />

caused a significant increase in the incidence of micronuclei .<br />

50869 3650

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