Environmental and Molecular Mutagenesis - Legacy Tobacco ...

1989 EMS Abstracts
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especially laryngeal carcinomas (Soskolne et al ., 1984 ; 1989 ; Beaumont et al ., 1987). Notes
Toxicologic evidence supgorts these human data and lncludes : a) in vivo and in vitro
cytogenetic abnormaliti6s following a sub-lethal decrease of extra-cellular pH ;
b) developmental toxicity as induced by acidic contaminants or drugs ; o) a crucial
role for pH in cell cycle, mitosis, and differentiation . The underlying biologic
mechanisms that explain adverse health outcomes include pH modulation of toxicity
for a number of xenobiotics (including carcinogens, genotoxins, and teratogens), and
low pH-induced changes of celle involving, for example, alterations in mitotic
apparatus and enzyme regulation . A•multi-disciplinary effort is prompted in order to
investigate the role(s) of environmental acids and acidic drugs in genotoxicity
and carcinogenesis . (Supported by the Italian Ministry of Health) .
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MITOMICIN C-INDUCED DOMINANT LETHAL MUTA't1VNS IN SYERMATOCYI'IiS ANS NOT DUE 1'0 CELL-
KILLING . J .P . Soto, F P va ivia, M .M . Orellana, N .M . Lafuente and H . Katob .
Facultad Odontologia, U . de Chile . STGO (CHILE) and Hatano Research Institute,
F .D .S .C ., Kanagawa (JAPAN) .
Mitosicin C(MC) is well known to induce doainant lethal autations in souse early spersatids and
speraatocytes but has not effect in late spereatids and spersatozoa (Ehling, 1971) and Kratochvilova
(1973) reported that MC cause high percent of unfertilized ova when MC-treatea anisals were sated at
intervals corresponding to treated speraatocytes, suggesting a strong cell-killing effect of MC to
speraatocytes . Histological studies and sperm head abnorsalities test ssre done to deteraine whether
MC-induced failure of fertilization in speraatocytes is attributable to cell-killing effect . 9 weeks
oid sale C('i aice were intraperitoneally (i .p) injected with 5 sg MC/kg . At 4 days intervals over a
7-week period following treataent, cauaal epididiaal spera and testes of 3 aniaals were recovered .
The nuaber of abnoraal spera head was 61 to 80 in the tiee points ranging froa 20 to 32 days post
treataent and increased to -200 in the tiae points 36 to 49 days after treatsent . At ail others,earliers,
tise points it was around the control nwber, i .e ., -10 abnorsal speras/1000 spera per anieal . The
abnoreal sperm frequency to tiae after treataent parallel the unfertilized ova frequency curve for
MC . In cross sections of testes tubules of these saae treated sice there was not evidences of cell-killing
in sperwtocytes ; therefore, spersatocytes developed to spersatids but there was faulty diffirentiation
of spersatozoa, rich appears to be a significant cause of failure of fertilization in sperutocytes .
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ANTIMUTAGENIC EFFECT OF PROSTAGLANDINE IN `HUMAN LYMPHOCYTE CULTURES
Sridevl,K . . K .P .Rao and K .V .Chandrika . Depariment of Genetics . Osmania University .
Ilyderabad-S00 007 . INDIA .
Prostaglandin E .(PGE) . is a derivative of -linolenic acid, an essential fatty
acid . PGE was tested for its antimutagenic activity !n invitro human lymphocyte
cultures . korbol myristate acetate (PMA) at 200ng/ml was used as the clastogen .
Whole blood cu,;tures were set up with Tc 1919 medium . Both the clastogen (PMA)
and PGE1 (10 M) were added at the synthesis phase of the culture (48 hrs) .
Cultures were harvested at 72 hours by hypotonic treatment followed by fixation .
Slides were prepared and 100 metaphases were scored for various chromosomal
aberrations like breaks . translocations . dicentrics etc . Three individual samples
were studied to minimize the sample variation . The frequency of chromosomal
aberrations was reduced with PGEI in PMA treated cultures, suggesting the protective
role of PGE3 .
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DETECTION OF MAMMALIAN CELL MD3AGENESIS IN AS52 CELLS . L .F . Stankowski, Jr ., W .G .
Tuman, M.J . Bieszczad and K .F . McLaren, Pharmakon Research International, Inc .,
Waverly, pA 18471
The AS52/XPRT assay is quite similar to the more familiar CHO/HPRT assay with
respect to its low spbntaneous mutant frequency and cytotoxic response to a variety of
agents . AS52 cells contain a single, functional, stably-integrated copy of the E . coli
qpt gene in a CHO cell line cont=ining a partial deletion of hprt, and have been used
to detect mutation of 5Wt (to TG ) under conditions identical to those for hprt in
CHO-KI-BH4 cells . Based upon the demonstrated or presumed carcinogenicity of
approximately 40 agents compared concurrently in the two assays, the AS52/XPRT and
CHO/HPRT assays exhibit sensitivities of 100 and 80%, and specificities of 94 and 100%,
respectively . Minor modifications further improve/simplify the AS52/XPRT assay . For
example, recalculation of survival data in terms of relative cell viability [(relative
cell density on Day) (relative cloning efficiency)1 provides a more accurate estimate
of cytotoxicity . Transfer of AS52 cells from MPA to XAT medium for 24 hours prior to
treatment prevents the poor growth occasionally observed after transfer to
unsupplemented Ham's F12 . The 7-day phenotypic expression time can be reduced, due to
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