Environmental and Molecular Mutagenesis - Legacy Tobacco ...

153
Clastogenic effects of ethyl-diamminedichbroplatinum in mice .
1 .Induction of ehromosomal aberration in Bone marrow cells .
A .E1-Tarras , A,N,Sharaf and N,A .Abdalla,
Dept . of Genetics, Fac . of Agric ., Cairo University, Cairo, Egypt .
The in vivo clastogenic effect of the anticancer drug ethyldiamminedich)
.roplatinum was investigated as chromosomal abersations
(CA) in the bone marrow cells of mice . Studies was carried out on F1
mice of the cross C3HX101 aged 12-14 weeks and weighted 25-30 gm .
The drug concentrations were 1,2 .5, 5 .0 .10,15 and 20 mg/kg at
duration time of 6,12 and 18 hours and the number of cells tested per
group is 500 cells . Results showed that 10 mg/kg dose was lethal
between 3 and 6 days while 15 and 20 mg/kg doses lethality oooured
within 24 hours . The percentage of cells containing CA without gap
for the doses 1,2,5 and 5 mg for 12 hours were 2,25%, 5 .25% and 8 .8%
respectively. However at 5 mg dose the CA persentage was 4 .2 at 6
hour interval while it was 2 .2, at 18 hours . These results indicate
that the clastogenicity of ethyl-platinum depends upon the stage of
cell cycle (S .p?iase) and it had a dose-dependant . Calculting the
doubling dose (DD) for clostogenic effects of ethyl-platinum in BM
was 0 .5 mg/kg . (Y a 0 .8 + 1 .6 D) .
154
POTENTIATING EFFECTS OF CAFFEINE ON MUTAGENICITY AND TERATOGENICITY
OF ALKYLATING AGENTS . M .M . E1-Zawahri and L .K . A1-Ghaith, Department of
Zoology, Faculty of Science, Kuwait University (Kuwait) .
A set of experiments was carried out to study the effect of caffeine
on the mutagenic and carcinogenic activities of EMS and MMS . Males
of D. melanogaster were fed or injected with 0 .5% caPfeine in sa11ne~~
before or after their treatment with a solution of 0 .1 mM EMS or M`15
in 10% sucrose for a period of 48h . The effects studied were dominant
lethals and sex-linked recessive lethals . Pre-treatment with caffeine
injection revealed a significant increase in the frequency of dominant
lethals but not of sex-linked recessive lethals induced by EMS or MMS .
Post-treatment of males with caffeine injection did not alter the frequency
of either of the two types of lethal mutations induced by MMS
or EMS . uhen 0-10h old males emerged from lardae reared on agar containing
0 .5% caffeine were treated with a solution of 0 .1 mM EMS or MMS in
10% sucrose, the frequencies of both dominant- lethals and sex-linked
recessive lethals significantly increased than of those untreated with
caffeine . These results indicate that caffeine may inhibit the repair
mechanism(s) of genetic damage induced by alkylating mutagens and this
may increase the mutagenic and teratogenic potentialities of such chemical
agents .
155
AUTOMATION OF SCREENING ASSAYS FOR DNA DAMAGING AGENTS WHICH INDUCE THE SOS
RESPONSE . R .K . Elespuru . Basic Research Program, NCI-Frederick Cancer
Research Facility, Frederick, MD 21701 .
The induction of the SOS response in E . coli is a physiological response to
DNA damage in which 20 or more genes are turned on . Unlike single gene
mutation, SOS induction is not a rare event and may be sean to occur in the
majority of an induced population . SOS induction may be monitored biochemically,
therefore, in a matter of hours after the event . Monitoring of
SOS-inducible genes has been facilitated by the fusion of these genes to jME,
the product of which, B-galactosidase, is expressed upon induction and is
easily monitored . Among SOS-inducible genes which have been fused to JM7,
and used for screening assays are lambda phage, &U and yQy . Two types of
colorimetric substrate-cleavage assays for B-galactosidase have been developed
which may be automated for screening purposes . One uses a soluble substrate ;
a miniaturied version of this quantitative assay may be performed in a∎ingle
microtiter well and may be automated using dispensers and plate readers . The
other, a spot test assay, uses a substrate generating an insoluble reaction
product ; this assay may be run like a semi-quantitative •dot blot• on petri
dishes to a dilution endpoint . For screening, several hundred samples may be
processed simultaneously on 243mm bioassay plates containing lawns of bacteria
and activating enzymes . Research sponsored by the National Cancer Institute .
DHHS, under contract No . NO1-CO-74101 with Bionetics Research, Inc .
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
1989 EMS Abstracts 55
Notes