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Environmental and Molecular Mutagenesis - Legacy Tobacco ...

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158 1989 EMS Abstracts 457<br />

Notes ~ -" IN VIVO IN<br />

'I<br />

TI~DS-TEST ON RAT HEPATOCYTFS EXPERIENCES IN TESTING XENOBiO-<br />

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

TICS AFTER SINGLE OR REPETITIVE TREATMENT .<br />

E .C . Puri, Th . _krtnowd D . MOlier, Ciba-Geigy Limited ., CH-4002 Basle (Switzerl<strong>and</strong>)<br />

The in vivo-in vitro DNA-repair test gained significance during the last years <strong>and</strong> was also performed<br />

in our laboratories for testing of chemical products as well as of the following reference compounds : 4aminobiphenyl<br />

(ABP), benzo(a)pyrene (BaP), dimethylnitrosamine (DMN), methylmethanesulphonate<br />

(MMS) <strong>and</strong> nafenopin (NAF). To investigate the effects of an enzymatic induetion of the liver a repetitive<br />

treatment with two of these compounds was also carried out . Therefore, compounds were administered<br />

either once (all five compounds), or repetitively (BaP, NAP). The preparation of hepatocytes<br />

(perfusion technique) followed 2 hours after the single application of ABP (200 mg/kg), DMN (15 mg/kg)<br />

or MMS (100 mg/kg) <strong>and</strong> 4 hours after the single application of BaP (100 mg/kg) <strong>and</strong> either 2 or 12<br />

hours after the single application of NAF (200 mg/kg). For the repetitive treatment the animals was given<br />

either BaP at a dose of 20 mg/kg or NAF at a dose of $00 ppm administered in the food on seven consecutive<br />

days, followed at the eighth day by a dose of 100 mg/kg BaP 4 hours before isolation of hepatocytes<br />

or by a dose of 200 mg/kg NAF either 2 or 12 hours before Isolation of hepatocytes . NAF did<br />

not induce DNA-repair synthesis under any of the treatment conditions . Several experiments with ABP .<br />

DMN <strong>and</strong> MMS yielded all clear positive results . BaP yielded a clear positive result after repetitive treatment<br />

. These positive results obtained with BsP after enzymatic liver induction by the test substance itself<br />

are noteworthy, inasmuch as earlier in vivo-in vitro experiments with the same substance on rat<br />

hepatocytes (Mirsalis et al ., 1982, Environm . <strong>Mutagenesis</strong> 4, 553), rat pancreatic cells (Steinmetz <strong>and</strong><br />

Mirsalis, 1984, Environm. <strong>Mutagenesis</strong> 6, 321) <strong>and</strong> rat tracheal epithelial cells (Doolittle <strong>and</strong> Butterworth,<br />

1984, Carcinogenesis S, 773), all performed without prior enzymatic induction, yielded negative results .<br />

458<br />

SOMiATIC NUTATIUN AND rtaCOMtlINA'TI0N TrST 0F FUnArYnINID0Nl ;, A Nr:W ANTIFILAaIAL AGEiVT,<br />

IN Dti0S0YHILA hh:LANOGASTan<br />

nei-Li Qian <strong>and</strong> A . F:iche<br />

Shanghai Institute of Pharmaceutical Industry, 1320 Beijing Xi rtoad, Shanghai, China<br />

Safety Assessment, Astra AS, S-15185, StidertRlje, Sweden<br />

The somatic mutation <strong>and</strong> recombination wing spot test in Drosophila melanogaater<br />

was used to evaluate the genotoxicity of Fluapyrimidone . Third inatar larvae, transhetero2ygous<br />

for recessive wing trichome mutationa were f6II food/test compound mixturea<br />

. A saturated solution or dilutions containing the test compound was added to<br />

Instant medium (cxp 1) <strong>and</strong> powdered Furapyrimidone was added to Yeast-Torula (&xp 2)<br />

at percentages of 0 .0j-S . F'urapyrimidone did not cause a significant change in the<br />

mutant spot frequency for any ty ;,e of spots in l:xp 1 . In Fxp 2, the frequency of large<br />

<strong>and</strong> twin spots was increased in flies treated with 0 .SdB Furapyrimidone . However<br />

in repeated experiment the differences were statistically insignificant . Fwrapyrimidone<br />

was positive on TA 100 <strong>and</strong> TA 98 at 0 .1 <strong>and</strong> 1 ntg/plate in Salmonella%microsome<br />

system for mutagenicity test but teat on Sex-linked recessive lethal test in Drosophila<br />

melanogaster Furapyrimidone showed no evidence of mutagenic potential .<br />

Acknowledgmente : This work was done at Safety Assessment, Astra AB . We wish to thank<br />

K . S<strong>and</strong>elin <strong>and</strong> G . idexell for their technical assistance .<br />

459<br />

1SICROt1UCLEUS TEST IN VICIA PAnA ROOT TIPS : INITAOR1tICITT OP COAL TAR PITCH . Z . Qingfan,<br />

ChangFuju, <strong>and</strong> Z . Qingxia . Dept . of Pathology, Henan Medical University . Zhengzhou,<br />

Henan, P .R . China .<br />

The effect of three different processed (high, moderate, low temperature) coal tar<br />

pitches on the induction of micronuclei in yjglg ZAbg root tips was studied . The results<br />

indicated that CTP had potent mutagenicity on'the root tips of y1gjA I&a, but the<br />

mutagenicity may vary in different kinds of CTP .<br />

TABLE . Frequencies of Micronucleated cells in }(jsL j4g root tips induced by CTP<br />

1oa1 ~ T,<br />

ar Pitch Croilp - maan3SD (a)<br />

Control Grouo<br />

Concentration (mg/ml) j, OZa =s<br />

0 .324 14 .33t0 .88 36 .33±4 .44 16 .33t0 .88<br />

(16 13 14) (38 43 38) (16 18 15)<br />

6 .828 39 .67t1 .76 59 .00±3 .46 26 .33t2 .91 1 .67±0 .67<br />

(39 43 37) (53 65 59) (27 21 31) ( 3 1 1)<br />

10 .0 60 .33±8 .08 82 .00t9 .61 60 .67±6 .49<br />

(49 76 56) (63 94 89) (58 73 51)<br />

These results are consistent with the study on rat lung cancera induced by<br />

intratracheal instillations of CTP, which were made by us previoualy, Through the<br />

experiment, we consider that the micronucleus test in yicig ZAg can be used as a new<br />

alarm system to detect envirorueental pollution such as CTP, <strong>and</strong> that this test has the<br />

advantages of sensitivity, reliability, low cost <strong>and</strong> manageability .<br />

50869 3672

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