Environmental and Molecular Mutagenesis - Legacy Tobacco ...

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AN SVALUATION OF TBB C90/BGPRT MUTATION ASSAY INVOLVING SOSPSNSION CULTURES AND SOFT
AGAR CLONING : RESULTS FOR 33 CHBKICALS . T . Oberly, M . Rexroat, s . Devsey, and K .
Richardson . Lilly Reseatrh Laboratories, Rli Lilly & Co ., Creenfield, IN 46140 .
The Chinese hamster ovary cell assay (C80) which measures forward mutation at
the BGPRT locus is utilized in several laboratories for the detection of mutagens . A
procedure involving treatment of CHO cells in suspension culture and mutant selection
in soft agar cloning has been developed (Oberly et al ., Mut . Res ., 18St99, 1987) . In
order to evaluate the effectiveness of these modHications, ff-chemMals representing
six chemical classes were tested, and the results were compared to findings obtained
with the additional assays "ployed in the battery of tests . A positive response was
obtained with 20 chemicals, all of_vhich are recognized sutagens . Of the 14
compounds that produced negative results, 4 were considered to be sutagens and/or
carcinogens . For example, the rat hepatocarcinogen methapyrilene was negative in the
CHO assay, and this finding agreed with all six test systems in the battery . In
contrast, the suspect carcinogen, 4-nitrobiphenyl, was negative in the C80 assay but
positive in 3 of 5 other test systems . Twelve of the compounds mentioned in this
report have been previously tested in other laboratories, and as a comparison, the
results reveal strong agreement between laboratories . These findings confirm that
the use of suspension cultures and soft-agar cloning in the CBO assay maintains the
sensitivity of the test in the discrimination of mutagens and is a viable alternative
to the traditional monolayer procedure of O'Neill et al . (Hut . Res ., 59 :109, 1977) .
In addition, the modified CHO assay has contributeT-to an overalrTsptovement in the
cost effectiveness for the assay which will be discussed .
420
SISTER-CHROMATID EXCHANGES AND CHROMOSOME ABERRATIONS INDUCED BY
CISPLATIN IN CULTURED HUMAN LYMPHOCYTES AND INHIBITORY EFFECTS BY
SODIUM THIOSULFATE .
T .Ohe, S .Tsuda*, Y .Sakata and T .Abe, Department of Hygiene and *Medicine,
Kyoto Prefectural University of Medicine, Kyoto 602(Japan)
Cisplatin(CDDP) is one of the most commonly used cytotoxic chemotherapeutic
agents, but has serious side-effects including renal and
haematological toxicities . On the other hand, it is known that CDDP
therapy combined with STS brings effective relief from such severe sideeffects
. In the present experiment, we examined the cytotoxicity,
SCEs and chromosome aberrations induced by CDDP in cultured human
lymphocytes, and in vitro interaction of CDDP4and STS on the frequencies
of SCEs and chromosome aberrations .
The mitotic index decreased ablyptly at 2 x_610-6 M and the yield of
SCES was dose-related between 10- and 4 x 10 M . A dose-dependent
increasg in frequency of chromosome aberra~ions w_is also found ug to
4 x 10 M . Simultaneous treatment of 10 - 10 M STS and 10 M CDDP
significantly reduced the number of CDDP-induced SCEs . Furthermore,
treatment of cells with STS 3-hr later after CDDP administration
significantly prevented toxicities as revealed by SCEs and chromosome
aberrations .
421
RELATION OF LIVER C:.RCItiOt~.A TO ENVIRONME.NTAL FdC':ORS IN A TROPICAL RAIN-BELT CITY .
:,.E . Ohwovoriole and G .C.E, Okeke, Dept . of Medicine, College of Medicine, University
of Lagos, LAGOS, ATGERIA .
Carcinoma of the liver is the commonest malignancy in many parts of tropical
Africa . The reasons for its high prevalence in many countries are not certain but
there are pieces of epidemiological evidence from other countries that environmental
factors may play a dominant role in the aetiology of liver cancer in the tropics .
Here we present an analysis of environmental factors in 104 patients with carcinoma
of the liver seen in a large tropical hospital in the rain belt of Nigeria . There
was a male predominance . Over 300 of the patients had historical or biochemical
evidence of serum hepatitis (hepatitis B virus infections) . About 30 to 40 percent
respectively gave a fairly strong history of alcohol and tobacco . A large rnanber of
the patients admitted to ingestion of local herbs in the form of concoctions . The
occurrence of ingestions of peanuts was no higher than in hospital controls .
Environmental factors appear to contribute significantly to the occurrEnce of
carcinoma in Lagos like in the rest of tropical Africa . However the sex ratio and
peak age differ somewhat from that reported from the northern part of the country .
The aetiology of liver carcinoma appears multifactorial . There is need to study
further the role of co-carcinogens or other mutagens besides hepatitis B virus in the
causation of liver carcinoma .
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
1989 EMS Abstracts 145
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