Environmental and Molecular Mutagenesis - Legacy Tobacco ...

106 1989 EMS Abstracts
Notes et a!. , Science, 236 : 933, 1987) . Thus, despite an earlier critique of these studies (Ray et al .,
Environ . Molec . Mutagen., 511 : 85, 1988), Ashby (Mutagenesis, 3 : 483, 1988) has suggested the
existence of 19 nonclastogenic mutagens based on these evaluations . To date (February, 1989), the
L5178Y/tk +/- mouse lymphoma assay (MLA) data on most of these 73 compounds have not been
published . For these reasons an effort was made to retest In a single laboratory two subsets of those
chemicals : those which had yielded marginal positive or negative results, and those proposed as possible
nonclastogenic mutagens . Six of the former (allyl Isovalerate, allyl Isothiocyanate, benzene, ethyl
acrylate, eugenol and geranyl acetate) and 7 of the latter (benzoln, benzyl acetate, chlorobenzene,
cinnamyl anthranilate, 1,2-dichlorobenzene, geranyl acetate (also on the marginal response list) and
sulfisoxazole) have been completed to date . Our results differ In 4 ways from those of the NTP : (1) we
saw little of the Inter- and intra-experimental variability seen In the original NTP studies ; (2) our
active dose ranges differed markedly for several compounds from those obtained in one of the contract
labs ; (3) we generally obtained significantly stronger mutagenic responses than did that same contract
lab, consistent with their weak MMS positive control responses : and (4) NTP's positive result for one
chemical (benzyl acetate) In the absence of S9 was not seen In these studies . The significance of these
results for test protocols, data evaluation, quality control, and assay correlations will be discussed .
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KINETICS OF DIMETNYLNITROSAMINE(Dl4d)-INDUCED MICRONUCLEUS (IQ1) FORMATION IN MOUSE BONE
MARROW AND SPLEEN CELLS . G . Krishna, M .L . Kropko, and J .C . Theiss, Parke-Davis Pharm .
Res . Div ., Warner-Lambert Co ., Ann Arbor, MI (USA)
The MN aasay has been extensively used in routine mutagen/carcinogen screening
programs to detect agents which cause chromosomal breakage and spindle dysfunction .
DMN is a known mammalian carcinogen and has been tested in both mouse and rat bone
marrow for its ability to induce MN . For D!'Qd, both positive and negative MN assay
results have been reported which may be due to differences in bone marrow sampling
times . The present study was disigned to obtain information on the kinetics of MN
formation following DMN treatment In mice . Groups of 3 to 5 CD1 male mice were
injected once i .p . with 50 or 100 mg/kg DMN . Both bone ∎arrow and spleen cells were
isolated at various sacrifice time-points (6, 12, 24, 36 . 48, and 60 h post-treatment)
and processed for MN analysis according to established procedures . Cyclophosphamide
(CP, 40 mg/kg) was used as a positive control and saline served as the vehicle
control . In the study, the vehicle control group had 0 .6 and 0 .9 !Q1/1000
polychromatic erythrocytes (PCEs) in bone .arrow and spleen cells, respectively . DMN
at 50 mg/kg, caused 3 .8, 7 .8, 8 .5 and 10 .2 !Qi/1000 PCEs in bone marrow and 8 .0, 9 .2,
19 .3 and 32 .8 AQJ/1000 PCEs in spleen at 12, 24, 36 and 48 h sacrifice times,
respectively . A similar time-related elevation of MN frequency was noted for 100
mg/kg DtQI . At each sacrifice time-point, spleen cells had a higher MN frequency
than bone marrow cells . In general . DMN caused a decrease in the proportion of PCEs
to normochromatic erythrocytes, suggesting toxicity . Thus, this study demonstrates
the clastogenic activity of DMN in both bone marrow and spleen cells of mice and shows
a time-related pattern in the elevation of DMN-induced MN frequency .
MI1rAGFr18, CARCItOMNS AND ANfI'1SkDUR AMTI5 IN '14tE INDIAN DIET
ARtM KRISf3171K[k1AR and V .M .SIVARN+Al62I
(Isotope Division, Cancer Institute,t ryr, Madras 600 020, INDIA)
The role of spices and other plant products wide consumed in India either
in the diet or in indigenous medicine, in relation to the alimentary cancers (oral,
gastric and oesophagal cancers) prevalent here, has been investigated with laboratory
animals . Most of the spices are found to be very well tolerated, even when
fed in large doses, with little change in physical appearance, growth rate or behaviour
.Cinnamon actually increases the growth rate . Out of the 25 plant products
screened,nine induced the carcinogen-detoxifying enzyme, glutathione-S-transferase,
in the st.omach, liver and oesophagus sufficiently high to be considered protective
agents . Ttrey are cunin (cLminum num) and poppy (Papaver aonniferrum) seeds ;
drumstick (Moringa oleifera), mana li (§21anun ni rwn) and (Ocinum basilicum)
leaves ; neem (Azadirachta indica) flowers ; asafoetida (Ferula asafoetida),
kandanthippili (pi lon ) and turmeric ((lrrctnna 1a a)9 Eight o t~.e . ,
excepting neem flowers, suppress the geno c e ects of 3,4-benzo(a)pyrene, when
simultaneously fed, cumin and poppy seeds being most effective . Feeding emblica
(phyllanthus emblica) decreases glutathione-S-transferase possibly a tumour-promoter
. Ames test reveals fried mustard, perandai (Cissus anr laris) and oil
of calamus (Acorus calartus) to be mutagenic ; tamarind (Tamar s indica) non-mutagenic
; while poppy s are antimutagenic .
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