Environmental and Molecular Mutagenesis - Legacy Tobacco ...

1989 EMS Abstracts
causes dissociation of 1-2 chromosomes, comparable to that caused by 0 .025 ug/ml Coloe- Notes
mid, producing aneuploid daughter eelle . The follicle ie avascular ; the oooyte in an
immature follicle is probably hypoxic because the capillaries in the surrounding theca
are few . Development of capillaries around a maturing follicle is determined by sex
hormones and angiogenlo factors, whose levels may be lower in the very young and the
older woman, and also occasionally in one of intermediate age . Exchange of gases
and other substances must take place through granulosa oelle and follioular fluid, so
the oocyte 02-C02 balance is dependent on an ample blood supply . Thus, a compromised
microciroulation could account for aneuploidy incidence in women of any reproductive
age, the frequency varying with the probability of events leading to reduced development
and/or funotion of the critical perifollioular capillary bed . The testioular tubule is
also avascular, so small localized regions of reduced circulation could result in•
aneuploidy . Lagging angiogenesis has been shown to cause bypoxic regions in tumors, so
reduced pH could be responsible for some of the aneuploidy seen in practically all
advanced tumors . Experiments in progress with mouae oooytes will be reported .
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SYMPOSIUM : CEOtOMOSOME ABERRATIONS :IMECHANISMS
MICRODOSIMETRY, LET AND CkQt0t4DSOMAL ABERRATICNS .
Charles R . Geard, Radiological Research Laboratory, College of Physicians and
Surgeons o Co umbia university, New York, N .Y . U .S .A .
Microdosimetry deals with the statistical fluctuations of energy deposition in
small volumes of irradiated matter . When applied to the cell nucleus or parts
thereof, the frequencies and intensities of different ionizing radiations can
be related to the induction of individual chromosomal changes . That is, a
relationship can be established between track based energy deposits and the
probability of lesion induction and interaction . It has been long established
that as linear energy transfer (LET) increases so does the likelihood of
biological effect . Currently this is particularly pertinent for the alpha
particle cellular traversals from radon daughters . At environmental levels of
radon, individual cells are very rarely likely to encountermmore than one
alpha particle . Therefore it is necessary to evaluate thromosomal changes in
individual cells on a per particle basis . To attain this end microdosimetric
evaluations of track events and of energy transfers in sub-nuclear volumes are
necessary in conjunction with morphometric assessments of cellular targets .
Over the LET range consistent with radon daughter alpha particles there is a
non constant probability of aberration induction both in terms of frequencies
and types of aberations . Hence assuming an equivalent status for these alpha
particles which are of profound societal concern is inappropriate .
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USE OF CYTOGENETIC STUDIES IN ASSESSING THE INVOLVEMENT OF MUTAGENIC AGENTS IN
PRELEUKAEMIC SYNDROMES AND ACUTE LEUKAEMIA . A .D .Geddes and A .Jacobs . Department of
Haematology, University of Wales College of Medicine, Cardiff, U .K .
The involvement of mutagenic/carcinogenic agents in the induction of preleukaemia
and acute leukaemia has been known for some time . Exposure may occur as a result of
chemo/radiotherapy or from occupational or environmental sources . Secondary leukaemias
are generally rapidly progressive with poor response to normal therapeutic regimes and
short survival . Cytogenetic characteristics include a high incidence of clonal
karyotypic abnormalities in the bone marrow (>85a) ; a high level of aneuploidy,
particularly chromosome loss ; high incidence of complex rearrangements including
unstable configurations such as rings, dicentrics, double minutes, etc and specific
involvement of certain chromosomes particularly 5 and 7 (66-90% of cases) . Cytogenetic
studies are therfore useful in the identification of mutagen induced disease and have
been used in Cardiff over the last 3 years to assess the potential involvement of
mutagenic agents in new cases of preleukaemia and leukaemia with no apparent history
of therapeutic or occupational exposure as well as monitoring those patients with a
history of prior therapy for other disorders or of occupational exposure to potentially
mutagenic agents . Studies included investigation of clonal karyotypic abnormalities
and aneuploidy in bone marrow and assessment of chromosome aberration levels in both
bone marrow and peripheral blood . Although such studies cannot prove a direct causative
role for mutagens in the development of preleukaemia/leukaemia they can provide
indications of mutagenic involvement and they may also assist in defining groups and
individuals at risk .
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