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82 1989 EMS Abstracts<br />

Notes Research supported by National Institute of General Medical Sciences (GM 09901) <strong>and</strong> by an<br />

Outst<strong>and</strong>ing Investigator Award from the National Cancer Institute (CA 44349) . References: Bohr VA,<br />

Phillips DH, Hanawalt PC, Cancer Res 47 :6426 . 1987 ; Hanawalt PC, Environ Health Pers 76 :9, 1987;<br />

Mellon I, Spivak G, Hanawalt PC, Cell 31 :241, 1987 ; Vos J-M, Hanawalt PC, Cell 30 :1789, 1987;<br />

Scicchitano DS, Hanawalt PC, Proc Nail Acad Se! USA : in press; Ho L, Bohr VA, Hanawalt PC, Mo!<br />

Cellu 8iol: in press.<br />

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

233<br />

ANTAGONISTIC EFFECT OF ASPARAGIIS ON DPIIi-INDUCED NICRONUCLEI AND APOPTOSIS IN THE COLON<br />

CRYPT CELLS OF NICE . S . Hanxiao, Z . Qingfan, A . Yuhui, F . Shuli, D . Guirong, Y . Bin,<br />

<strong>and</strong> W . Yongjun . Dept . of Pathology, Henan Medical Univ ., Zhengzhou, Henan, P .R . China .<br />

The effect of asparagus on micronuclei <strong>and</strong> apoptosis in the colon crypt epithelial<br />

cells of mouse induced by Dimethylhydrazina (Dt41) was studied . Four groups (5 mice/group)<br />

were intraperitoneally injected with D141 solution, among which three groups were treated<br />

with oral liquid asparagus in the volume of 0 .1, 0 .5 or 1 ml per mouse, respectively, by<br />

stomach intubation one hour prior to injection . The fifth group was injected with 1mM<br />

EDTA intraperitoneally as the control . Twenty four hours after injection, all animals<br />

were sacrificed . The maximum number of micronuclei <strong>and</strong> apoptosis were observed in the<br />

DMH alone group . All three groups of oral liquid asparagus mice had lower incidence of<br />

micronuclei <strong>and</strong> apoptosis than Dt4t alone treated animals, <strong>and</strong> showed a positive doseeffect<br />

relationship . The results indicated that asparagus has antagonistic effect on the<br />

mutagenicity of colonic carcinogens .<br />

TABLE . Number of Micronuclei <strong>and</strong> Apoptosis in Colon Crypt Cells (p < 0 .01)<br />

Mean M of lt .A_/ Mean N of lK .A ./<br />

Cx=t of Each Nouse Crypt of Each Grouo<br />

Crouv 1 2 3 4 5<br />

DMH 4 .05 3 .80 3 .50 4 .15 4 .45 3 .99<br />

1 ml 0 .80 0 .70 0 .70 1 .00 0 .60 0 .76<br />

0 .5 ml 1 .90 1 .85 1 .15 1 .35 1 .50 1 .55<br />

0 .1 ml 2 .85 2 .30 3 .20 2 .55 2 .65 2 .71<br />

EDTA 0 .45 0 .30 0 .65 0 .35 0 .45 0 .42<br />

234<br />

MUTAGENICITY STUDIES ON FENITROTHION IN BACTERIA AND MAMMALIAN CELLS .<br />

M . Hara, S . Kogiso, F . Yamada, M . Kawamoto, A . Yoshitake <strong>and</strong> J .<br />

Miyamoto, Biochemistry <strong>and</strong> Toxicology Laboratory, Sumitomo Chemical<br />

Co ., Ltd ., Osaka, Japan .<br />

The mutagenicity of fenitrothion was determined in strains of<br />

Salmonella ~t h~imurium <strong>and</strong> Escherichia coli . Fenitrothion was found to<br />

be non-mutagenic in Salmone la t mur~um strains of TA98, TA1535 <strong>and</strong><br />

TA1537 <strong>and</strong> in Escher c WP uvrA both with <strong>and</strong> without S9 mix,<br />

while weak mutage t~y was observ-eT-only in TA100 strain <strong>and</strong> enhanced<br />

by the addition of S9 mix . The mutagenicity observed in the TA100<br />

strain was not expressed in a nitroreductase-deficient strain, TA100<br />

NR, <strong>and</strong> decreased in a transacetylase-deficient~strain TA100 1,8-DNPG<br />

The mutagenicity of fenitrothion was also examined by a gene mutation<br />

assay using the gene for hypoxanthine-guanine phosphoribosyltrangferase<br />

(hgprt) in V79 Chinese hamster lung cells . Fenitrothion<br />

did not induce any increment of 6-thioguanine-resistant mutant cells<br />

at doses ranging from 0 .01 to 0 .3 mM regardless of the presence or<br />

absence of S9 mix . The results suggest that reduction of fenitrothion<br />

by a bacterial nitroreductase of TA100 to an active form is essential<br />

for the expression of the mutagenicity of fenitrothion in TA100 <strong>and</strong><br />

that a bacterial transacetylase of TA100 also has an important role in<br />

the process of mutagenic activation .<br />

235<br />

EVALUATION OF SEVERAL ANTINEOPLASTIC DRUGS IN THE IN VITRO UNSCHEDULED DNA<br />

SYNTHESIS ASSAY. P.R. Harbach, S .K . Wiser. A .L. Smith <strong>and</strong> C .S. Aaron . The Upjohn Co .,<br />

Kalamazoo, MI 49007<br />

The in vitro unscheduled DNA synthesis (UDS) assay in rat primary hepatocytes is an<br />

essential part of the genetic toxicity at The Upjohn Company (TUC) . This assay detects the<br />

repair of damage to rat hepatocyteDNA caused by a wide variety of mutagens <strong>and</strong><br />

carcinogens. Primary hepatocytes were dissociated from the liver <strong>and</strong> placed into<br />

monolayer culture which was incubated with the test <strong>and</strong> control compounds <strong>and</strong><br />

labelled thymidine for 16-20 hours . The cultures were fixed, <strong>and</strong> the incorporation of<br />

thymidine was measured by autoradiogrsphy . The results were expressed as net<br />

grains/nucleus (NG) . We have tested several antineoplastic dru s in the UDS assay :<br />

tetraplatin (U-77,233) cis-platinum, m-AMSA, CC- 1065, U-73,97~<strong>and</strong> menogaril . The<br />

latter three compounds were developed by TUC . U-73,975 is an analog of CC-106S which<br />

50869 3594

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