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Environmental and Molecular Mutagenesis - Legacy Tobacco ...

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196 1989 EMS Abstracts<br />

~ . . .r -- . ..<br />

Notes- -<br />

.$c~ .-{~im id's Micromuel~eu.cs Test . Nine to 10 weeks old Strong A male mice were<br />

separately treated i,p with 2 mutacarcinogens : dimethylnitrosamine(DMN),<br />

10 mg per kg_$_V,_~mitomycin C (mito C),3 mg per kg BW . An hour after<br />

injection of the mutacarcinogens,pheno,90 *g per kg BW <strong>and</strong> sac,2 .S gm per<br />

kg BW were given to the animals treated with mutacarcinogens via the<br />

same route . Pheno was injected to the DMN-treated group <strong>and</strong> sac to the<br />

group receiving mito C . Bone marrow cells from femora of animals were<br />

isolated using fetal calf serum for suspension . Cells were collected by<br />

low speed centrifugation <strong>and</strong> smears prepared . Slides were stained using<br />

May Grunwald-Giemsa stain, Animals that received pheno <strong>and</strong> sac after injection<br />

with mutacarcinogens showed -inereased production of micronuclei .<br />

The mito C-sac combination showed peak micronuclei formation when sac was<br />

given 3h after injection of mito C . Statistical analysis showed significance<br />

at p= .05 . Results agree with earlier studies showing increased germ<br />

cell toxicity of DMN <strong>and</strong> mito C after treatment with pheno <strong>and</strong> sac . Both<br />

findings suggest that pheno <strong>and</strong> sac could exert their cancer-promoting<br />

actions by enhancing the mutagenicity of mutacarcinogens in somatic as<br />

well as germ cells . Whether all cancer promoters act in like manner<br />

remains to be seen,<br />

GENOTOXIC ACTIVITIES OF 3-CHLOROPROPIONIC ACID AND RELATED COMPOUNDS<br />

M . SZEGEDI<br />

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

Chemical Works of Gedeon Richter Ltd . Microbiological Research Laboratory<br />

H-1475 Budapest, 10 . P .O .B . 27 . Hungary<br />

The 3-cloropropionic acid (3CPA) has a strong genetoxic activity<br />

in Salmonella typhimurium TA 1535 nd TA 100 strains . We have tested<br />

a group of chemicals - withouth metabolic activation - in the E .coli<br />

SOS chromotest . They were similar to 3CPA different in the lenght of<br />

the carbon chain <strong>and</strong> the subtituens as follows : propionic acid,<br />

propionyl chloride, 2-chloropropionic acid, 3-chloropropionic acid,<br />

2-chloropropionyl chloride, 3-chloropropionyl chloride, chloroacetic<br />

acid, 2-chioropropane, 1-chlorobutane, 4-chloro-l-butanol, 1-chloropropane,<br />

1-chloro-2-propanol, 3-chloro-propionitrile,<br />

3-chloropropionitrile . The experiments were carried out in BIOSCREEN<br />

Analyzing System using BIDSOS program (LABSYSTEMS Ltd .) . Positive<br />

response was given only by 3CPA <strong>and</strong> 3-chlorpropionY1 chloride<br />

suggesting that C1-CH2-CH2C0- is resposible for activity .<br />

569<br />

570<br />

EVALUATION OF THE CLASTOGENIC ACTIVITY OF ROCBAGAN (BENZNIDAZOLE) IN<br />

MAMMALIAN SYSTEMS .C .S .Takahashi,S .C .Souaa <strong>and</strong> S .J .Santos, F .F .C .L .R .P .,<br />

USp <strong>and</strong> F .M .R .P .,USP,Ribeirao Preto,Sao Paulo,Brazil .<br />

Rochagan, a drug whose active compound is benznidazole(N-benzil-2 ni<br />

tro-l-imidazolacetamida), is used for the treatment of Chagas'disease<br />

<strong>and</strong> has been effective as a trypanosomicide . The drug was tested for<br />

clastogenic activity in Wistar rats treated by gavage at doses of 50 to<br />

1000 mg/kg body weight administered three times at 8 h intervals <strong>and</strong> in<br />

human lymphocyte cultures at doses of 250 pg/ml culture medium .Six rats<br />

were used in each treatment <strong>and</strong> sacrificed 6, 12 <strong>and</strong> 18 h after the<br />

last treatment . One hundred bone marrow metaphase cells per animal were<br />

analyzed for chromosome aberrations,showing frequencies similar to control<br />

values for all treatments (0 .30 to 1 .66Z) . For the in vitro test,<br />

blood was obtained from 5 healthy donors <strong>and</strong> benznidazole wasa ded at<br />

the beginning of culture .One hundred metapbases per individual were ana<br />

lyzed for chromosome aberrations <strong>and</strong> 50 metaphases for SCE . The frequen<br />

cies of chromosome aberrations <strong>and</strong> SCE were 3 .2x <strong>and</strong> 8 .01 SCE/cell in<br />

control cultures <strong>and</strong> of 62 <strong>and</strong> 13 .89 SCE/cell in treated cultures .A<br />

slight increase in SCE was observed in the treated group .The lack of<br />

positive results could be explained by the absence of reduction products<br />

. These reactive metabolites were observed under anaerobic conditions<br />

which does not occur in the systems used .<br />

50869 3710

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