Environmental and Molecular Mutagenesis - Legacy Tobacco ...

22 1989 EMS Abstracts
Notes
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
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STUDIES ON MUTAGENIC AND ANTIMUTAGENIC EFFECTS OF COBALT (1l) CHLORIDE
IN SWISS MICE
H .N . Bhilwade, R.C. Chaubey and P.S. Chauhan, Molecular Biology and Agriculture Division,
Bhabha Atonic Research Centre, Bo-nbay 400085 .
Cobalt (1l) chloride has been reported to inhibit the m utagenic effects of ionizing radiation
aaj chan ical m utagens in prokeryotic systen s . Lack of a s'm ilar study in m amm als, which
are more relevant for investigations on genotoxic prevention in man, prvnpted us to examine
the ability of cobalt (11) chloride to modify the clastogenicityof a chemical mutagen methyl
m ethanesulfonate (MMS) and ionizing radiation (gamm a rays) using bone m arrow m icronucleated
cells in mice. Cobalt (Im) chloride at a single dose of 15.0 mg/kg provoked a mild increase
in the frequency of micronucleated polychro~natic erythrocytes (MN-PCEs ` over controls
which increased further at 30 and 60 mg/kg dose (p< 0.05). There was, however, $ lack
of dose-response relationship . Pretreahn ent of m ice with a single dose of 45 m g/kg of
cobalt (ll) chloride reduced the frequency of MMS induced MN-PCts, significantly . Exposure
of mice to 15.0, 30.0, 45.0 and 60.0 mg/kg of cobalt (lI) chloride showed a dose dependent
decrease in the levels of MN-PCEs in cvnparison with MMS alone. A moderate but significant
(p e 0 .05) reduction in the frequency of MN-PCEs in gamm a Irradiated (1 .0 Gy) m ice was
also observed at 30 .0 mg/kg of cobalt (1I) chloride. The multiple dosage reginen of cobalt
(il) chloride were not of much consequence .
NUTAGENICITY OF ORGANIDINo AND ITS MAJOR COMPONENT, 3-IODO-1,2-PROPANEDIOL
J .B .Bisho ,K.L .Mitt,E .Zeiyer,J .Mason,N .D .Shelby, and J .E .French, NIEHS,RTP,N .C .
ryan inm [5634-39-9], is an expectorant found in OTC cough preparations . In
NTP 2-year rodent studies, it induced leukemias and thyroid tumors in male rats,
and pituitary and harderian gland tumors in female mice . Organidin is mutagenic in
bacterial and mamnalian cells . In contrast to the patented formulation, Jameson, et
al .(1988) reported that Organidin consists of 33% 3-iodo-1,2-propanediol (IPO), 17%
glycerol, 40% polymers of glycerol, iodo-plycerol and numerous
other components, of which -10% were isomeric p-dioxanes . Jones (1975) purported
metabolism of IPD to the mutagenic epoxide, glycidol ; therefore, we have examined
the in vitro and in vivo genetic toxicity of Organidin, IPD and glycidol to better
understand the bases of Organidin's mutagenic and carcinogenic activity . None of
the 3 chemicals required exogenous metabolic activation in the bacterial strains or
mammalian cells in which they were active . Organidin was muta9enic in base substitution
strains of Salmonella (TA100 and TA1535) but not in frame shift strains
(TA97 and TA98) ; glycidol was mutagenic in both base pair and frame shift strains
(TA100, TA1535, TA1537, TA97 and TA98) (Cantor et al .1986) ; IPD, like Organidin,
was mutagenic in TA100 but not TA98 . All 3 chemicals induced SLRL mutations In
Drosophila (Glycidol>IPD>Orqanidin) . Glycidol and Organidin both induced ABS and
SCE in CHO cells (Glyctdol>Or9anidin) . IPD is on test In CHO . Glycidol was weakly
positive in a bone marrow micronucleus test using B6C3F1 mice, but IPD and
Organidin were negative . The relevance of these responses to understanding the
mutagenic and carcinogenic effects of Organidin will be discussed .
NONACTIVATED MVfAGENICITY OF CHEMICALLY NITRATED OILS CORRELATES VITH S-9-DEfENDEPr['
ACTIVITY OF THE UNMODIFIED OIL IN THE AMES ASSAY . G .R . Blackburn, R .A . Deitch , S .E .
IRVIN , C .A . Schreiner, and C .R . Mackerer , Mobil Environmental & Health Science
Laboratory, P .O . Box 1029, Princeton, NJ 08540 .
Previous studies In this laboratory have shown that modifications to the sampledelivery
and activation procedures in the Ames Assay lead to a substantial increase
in the correlation between mutagenic and dermal carcinogenic potency of petroleumderived
materials . An adjunct method, providing equal predictability, but requiring
no S-9 preparation, and hence no sacrifice of animals, relies upon preliminary
chemical nitration of oil samples, followed by assay in atrain TA98 . One hundred ul
aliquots of oil are nitrated in 70 X(v/v) nitric acid at 80°C, for 90 ∎in . The
nitrated derivatives are extracted into dichloromethane, concentrated, and resolubilized
In DMSO for testing . Doses equivalent to 2, 1, 0 .5, 0 .1, and 0 .05 ug
oil/plate generate dose-response curves with slopes ranging from 0 to 500 revertants/ug
. The correlation between slopes from the nitration method and the S-9
dependent assay for 30 oils is 0 .85 (r), and between the former and the relative
carcinogenic potency (reciprocal of the mean latent period to tumor formation) is
0 .92 (27 oils) . Neither method provides reliable predictability for oils boiling
under 500°F, apparently because many of these materials are not genotoxici the nitration
method is further limited at the high end of the distillation range for
petroleum, i .e . fractions boiling above about 900•F . The simplicity of the method
makes possible the evaluation of as many as 20 oils in one assay, at very low rnet
per sample .
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