Environmental and Molecular Mutagenesis - Legacy Tobacco ...

234 1989 EMS Abstracts
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http://legacy.library.ucsf.edu/tid/clb93d00/pdf
Notes which have been i'Nntified as toxicants and those whose biological effects are not
yet known . While, literAfare is replete with reports showing a number of dietary components
to be mutag'enit;^-=tirrent information on inhibitors of mutagenesis has been
recently reviewed (DsFlora, ed ., Mutation Res . 202, No .2, 1988) . However, majority
of the investigations on antimutagenesis vis-a-vis mutagenesis have emerged from bioassays
using prokaryotic systems . While, this information provides a basis for further research
and these assays are suitable for mechanistic studies, the results cannot be directly
extrapolated to human system . In our laboratory, inhibitory effects of dietary factors
including vitamins and trace elements, on chemical and radiation mutagenesis have been
investigated in somatic and germinal cells of mice, These whole animal studies, though .
support some of the observations emanated from prokaryotes, divergences are apparent
between the two systems . It is pointed out that the ability of a putative inhibitor
to survive the physiology of the mammalian gut, its absorption and availability in
biophase would greatly contribute to its effectiveness in vivo . It is also evident that
any programme on dietary prevention of genotoxicity wou~t-embark upon, removal of
mutagens from the diet and incorporation of inhibitors of mutagenesis . Such a dietary
reciepe, if ever formulated will have the advantage of allowing intervention at the
community and public health level .
ENVIRONMENTAL MUTAGENESIS IN DEVELOPING COUNTRIES
C . cortinas de Nava, instituto de Investigaciones siomidicas, U .N .A .M .
Ap . Postal 70228, Mexieo 20 D .B ., 04510 Mexico .
The term developing countries encompasses a wide variety of situations
: geographical, economical, politioal, soeial, eultural, ete . . A
common denominator of those countries is the need to optimise efforts
to stop environmental deterioration and diminish the impact of chemical
pollution on human health and the eoosystems . This mplies the nesd of
programs for integral evaluation of environmental pioblems, a~iequate -
technologies for their control, a rapid multiplication ef 1ooa1 experts
in the field, integration of multidisciplinary research groups and the
community participation in activities of environmental protection and
prevention of health risks . Genetic Toxicology in developing countries
can only contribute sustantielly to these goals if it is incorporated
to the global actions intended to set priorities,to characterize and -
manage the environmental risks . Collaboration of scientists from develoM+d
countries 1a needed to speed theet, aot•lons, 'in partieul+ir, thnna
concerning training of personnel, development of technol0q ies and information
exchange . In addition, the establishment of collaborative -
research projects to evaluate and control environmental problems of -
regional interest will make the efforts of scientists from devaloping
countries, working on the field, more relevant .
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681
Transgenic mice as a model system for studying gene mutations in vivo .
Jan A . Gossen, W .F .J . de Leeuw, C .H .T . Tan and Jan Vijg, TNO Institute
for Experimental Gerontology, P .O . Box 5815, 2280 HV Rijswijk, The
Netherlands .
In order to study gene mutations in different organs and tissues of an
experimental aniT .al, we constructed transgenic nice harbouring
bacteriophage 1a^:bda shuttle vectors integrated in the qeno^ :e in a headto-tail
arrangement . As a*.arazt fcr rnutagenesis, the selectable
bac*.erial LacZ aene was cloned in the vector . The integrated vectors were
rescued fror total genonic DN1, with high efficiency by in vitro packaging
and propagation of the phages in an E .cc C Lac2- strain . This systex
allowed the detection of :-.utation frequencies down to about 5 .10-6, the
background frequency in different organs . Treatment of adult fenale
transgenic :rice with fi- ..thyl-N-nitrosourea (ENU) resulted in a dosedependent
increase of the mutation frequency in the vectors isolated fro^t
brain D!tA, up to 10-1 at 250 :^g E1N per kg bodyweight . At this dose, in
liver and bone -arrow Dtd:A of the sa :^e :r:ice, mutation freyu_ncies were 2 .9
}: 10-' ar.d 8 .5 . . 10-°, respectively . Restriction-enzyme analysis
indicated that the mutations observed in the LacZ target gene were point
mutations (