Environmental and Molecular Mutagenesis - Legacy Tobacco ...
Environmental and Molecular Mutagenesis - Legacy Tobacco ...
Environmental and Molecular Mutagenesis - Legacy Tobacco ...
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F<br />
140 1989 EMS Abstracts<br />
Notes EFFECT OF GLUTATHIONE ON MITOMYCIN-C IN SWISS ALBINO MICE AND HUMAN LY1pNDCYTES<br />
RITA NARAM . D . GsethanJali <strong>and</strong> P .P. R@My<br />
Institute of Genetics Hospital for Genetic Disaases . owania Universitv . Baauaoet . Hvd.rabad-300 016 .<br />
A.P . India .<br />
AWIMOT<br />
Mito,yc in .C (MMC) is a potent antibiotic with autayenic <strong>and</strong> antitumor activity presusably through<br />
its covalent binding to DNA. MMC was tested for its autapanic potential in the presanca of plutethiona<br />
(GSH)in invivo <strong>and</strong> invitro systas .<br />
404<br />
Swiss albino .ice were fed orally with 2s0/Kp . b .w. M(C <strong>and</strong> 20.40 .80 <strong>and</strong> 160 ap/kR b .w . GSH slmultaneously<br />
to four groups of anLsals . The doses were administered at 0 hrs <strong>and</strong> 24 hrs . 6 hrs after the second<br />
dose the animals wra killed <strong>and</strong> aicronucleus test was dona as described by Schsid (1973) . Ll.phocyte<br />
cultures ware initiated fros healthy donors <strong>and</strong> 0 .2 uylUl MMC <strong>and</strong> 2 .5 . 5 .0 . 10 .0. 10 .0 <strong>and</strong> 20 .0 up/al<br />
GSH was added simultaneously to four se-ts of cultures . 72 hrs after treataant the cultures were tenli-<br />
neted <strong>and</strong> slides ware prepared as described by Moorhead et al ( 1960) . Thare was a significant decreese<br />
in the frequency of aicronuclei !n young erythrocytes <strong>and</strong> chroaosasal ebearrations in lyaphocytes<br />
treated with MMC in casbination with OSH when coapered to MMC alone .<br />
405<br />
EFFECT OF NICOTINAMIDE ON HEPATOTOXICITY ASSOCIATED WITH CARBON TETRACHLORIDE,<br />
BROMOBEN2ENE AND ALLYL ALCOHOL, L .M .Narurkar, J .P .Ramat, S .J .D'Souza, R .Krishnamoorthy<br />
& M .V .Narurkar, Biochemistry Division, Bhabha Atomic Research Centre,<br />
Bombay, India .<br />
Recurrent toxicity with cell necrosis resulting in regenerative stimuli has been<br />
proposed as one of the mechanisms of tumour promotion . Tumour promoters which are<br />
usually hepatotoxic agents may bring about selective inhibition of the cytochrome<br />
P-450 dependent microsomal drug metabolizing enzymes . It was observed that administration<br />
of tumour promoting <strong>and</strong> hepatotoxic agents such as carbon tetrachloride<br />
(0 .2 ml/kg .b .w .), bromobenzene (0 .2 ml/kg . b .w .) <strong>and</strong> allyl alcohol (30 mg/kg . b .w .)to<br />
rats brought about a significant inhibition of hepatic mixed function oxidase<br />
(MFO) system, while the conjugating UDP-glucuronosyl transferase activity was<br />
increased . The serum glutamate-oxaloacetate transaminase <strong>and</strong> serum glutamatepyruvate<br />
transaminase activities were also highly increased followin~ administration<br />
of these toxic agents . Further, when nicotinamide (250 mgs/kg . b .w. , an endobiotic<br />
shown in our laboratory to be an inducer of MFO, was administered simultaneously to<br />
rats along with hepatotoxic agents in independent experiments, the biochemical toxic<br />
manifestations were significantly modified . Besides the MF0 inducing ability,<br />
nicotinamide has been shown to bring about stabilization of polysomes as evidenced<br />
by marked reduction in monomers <strong>and</strong> dimers with simultaneous increase in the heavier<br />
aggregates, increase in total polysomal RNA accomganied by decreased alkaline RNase<br />
activity as well as enhanced incorporation of 1 C-leucine pulse in the ribosomal<br />
aggregates .<br />
406<br />
COMPARISON OF SISTER CHROMATID EXCHANGES IN SPLEEN AND THYMIC LYMPHOCYTES FROM AKR,<br />
B6D2F1 AND CBA MICE FOLLOWING IN VIVO EXPOSURE TO N-NITROSO-N-METHYLUREA . R .E . Neft,<br />
H .M . Schol <strong>and</strong> D .A . Casciano, National Center for Toxicological Research, Jefferson .<br />
AR 72079<br />
In order to evaluate the ability of the in vivo/in vitro murine lymphocyte sisterchromatid<br />
exchange (SCE) assay to predict carcnicity . SCE induction by N-nitro-<br />
N-methylurea (MNU) was studied in spleen <strong>and</strong> thymus lymphocytes from ARR mice which<br />
are highly susceptible to MNU-produced thymomas, CBA mice which are much less sensitive<br />
to induction of thymomas by MNU, <strong>and</strong> B6D2F1 mice . Following a single i .p . injection<br />
of 0 .033, 0 .066, 0 .131 mmol/kg MNU or PBS (vehicle control), clear dose-related<br />
increases in SCE were observed in LPS-stisulated spleen lymphocytes <strong>and</strong> Con A-stimulated<br />
spleen <strong>and</strong> thymus lymphocytes from ARR, CBA <strong>and</strong> B6D2F1 mice at 1 <strong>and</strong> 24 hours<br />
post-exposure . In general, MNU-induced SCE were higher in Con A-stimulated spleen<br />
lymphocytes compared to LPS-stimulated spleen lymphocytes <strong>and</strong> Con A-stimulated thymas<br />
lymphocytes from each mouse strain . On the whole, MNU-produced SCE were lower in<br />
AKR <strong>and</strong> CBA spleens than in B6D2F1 spleens . In addition, for the most part, l4iUinduced<br />
SCE levels in thymus lymphocytes from all three strains of mice were similar .<br />
In the present study, differences in MNU-induced genotoxicity in ARR, CBA <strong>and</strong> B6D2F1<br />
thymus lymphocytes could not be ascertained by use of the in vivo/in vitro SCE assay .<br />
(<br />
r<br />
F 50869 3654<br />
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
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