Environmental and Molecular Mutagenesis - Legacy Tobacco ...

442 = 1989 EMS Abstracts 153
Notes
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HUMAN DNA ADDUCTS DUE TO SMOKING AND OTHER CARCINOGEN EXPOSURES .
D .H . Phillips, Institute oftancer Research, Chester Beatty Labs, London, UK .
Human exposure to complex mixtures of potentially carcinogenic polycyclic
aromatic hydrocarbons (PAH) has been monitored by 32P-postlabelling analysis of
DNA isolated from human tissues . The presence of aromatic adducts in DNA from
peripheral lung has been detected at levels proportional to the numbers of
cigarettes smoked by the individuals . The complexity of the adduct patterns
indicated that adducts were formed by-$ large number of different compounds . Lung
DNA from former smokers of several years' abstinence generally showed a level of
adducts similar to that in DNA from non-smokers . Analysis of bronchial DNA also
revealed evidence of smoking-related adducts . Adduct levels in peripheral blood
lymphocyte DNA did not differentiate between smokers and non-smokers .
Occupational exposure to PAH amongst iron foundry and coke oven workers was,
however, evident from the elevated levels of PAH-DNA adducts in their lymphocyte
DNA compared to levels in unexposed control subjects . Exposure of human skin to
PAH, monitored in psoriasis patients receiving topical applications of coal-tar and
juniper tar, leads to the formation of adducts in this tissue . Corroborative studies
on the formation of adducts in experimental animals provide further evidence of
the potential carcinogenic risk to humans of exposure to these PAH mixtures .
443
CHROMOSOME-SPECIFIC PROBES IN CYfOGENETICS . D. Pinkel, J. Gray, R. Segraves, J. Lucas, W-L.
Kuo, B . Trask, L C. Yu, D. Eastmond, M. Poggensee. Lawrence Livermore National Laboratory,
Livermore Ca . 94550 .
Cytogenetic analysis now relies primarily on staining procedures that produce patterns of bands on
metaphase chromosomes. Analysis of these bands by skilled observers permits chromosome identification
and recognition of structural and numerical aberrations. However the proce4ures are time
consuming and limited to mitotic cells . Recent developoments in chromosome stainEng by in situ
hybridization promise to extend cytogenetic analysis to new areas . Since staining is based on DNA
sequence, the staining pattern can be tailored by the choice of probes, and information can be obtained
from complex settings such as interphase nuclei . Two classes oj probes have proven useful . The first
are probes for chromosome-specific repetitive sequences . These sequences occur in compact clusters,
frequently near the centromeres . Specific probes for approximately 2/3 of the human chromosomes
are known. Nuclei hybridized with these probes show a compact spot at the location of the target
sequence, permitting identification of aneuplold cells . The second class of probes, composite probes,
consist of collections of probes which produce a desired staining pattern on chromosomes . Composite
probes capable of staining a specific chromosome type over its entire length are now available for all of
the human chromosomes. They permit rapid detection of structural abnormalities such as translocations
in metaphase spreads and interphase nuclei. In situ hybridization with probes of both types
has allowed us to detect aneuploidy induced by in vitro chemical exposure, trisomy 21 and other
important prenatal numerical abnormalities, and translocations induced by in vitro and in vivo
radiation exposures . Work performed under the auspices of the USDOE by the LLNL under contract
W-7405 ENG-48 and USPHS grants CA45919, GM25076, and HD17665 .
444
ENHANCED REACTIVATION AND NUTAGENESIS OF ADE 2 VIRUS IN CARCINOGEN -
PRETREATED BELA CELLS
Stelios N . Piperakis
Institute'of Biology, N .R .C . "Democritos"
Agia Paraskevi, Athens - Greece
Enhanced reactivation of a UV - irradiated mammalian virus by pretreatment
of susceptible host cells with a number of agents has now been
found to exist in different systems . In many studies with mammaliancells
an increased degree of viral mutagenesis has also been found with increasing
damage to the virus,but there is still disagreement as to whether
this mutagenesis is further enhanced by pretreatment of the cells .
In the present study an investigation has been undertaken in the Ade 2-
Hela system . Hela cells were treated with the agents sodium arsenite,
EMS, and aflatoxin Bland the enhanced reactivation and enhanced mutagenesis
of UV - irradiated Ade 2 was compared to the enhanced reactivation
and enhanced mutagenesis obtained by UV, heat and MMS .
The results show that the enhanced reactivation of UV-irradiated Ade 2
observed in Hela cells pre-treated with these agents is not due (at
least under the used experimental conditions) to the induction of an
error - prone DNA repair mechanism .
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