Environmental and Molecular Mutagenesis - Legacy Tobacco ...

1989 EMS Abstract s
sufficient for measurement of the spontaneous mutation rates in whole Notes
animals . Mutations are detected by monitoring the activity of a
P galactosidase target gene contained within the lambda genome . The
high rescue efficiency is accomplished through the use of methylated
cytosine restriction deficient (mcr ) lambda packaging extracts and
plating strains. This mutagenesis assay will permit comparison of
mutation rates between different tissues in whole animals . In
addition, the shuttle vector is being modified to include the in vivo
excision features of the lambda ZAP cloning vector. This will
facilitate the DNA sequencing for identification of the sequence
specificity of genotoxic substances .
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SCHISTOSOMIASIS DRUGS : AN ICPEMC STUDY
P .G .N. Kramers (1), J .M. Gentile (2), B.J .A .M. Cryseels (3), P . Jordan (4), N. Katz
(5), K .E . Mott (6), J .J . Mulvihill (7), J .L. Seed (8), and H. Frohberg (9) ; (1)
National Institute of Public Health and Environmental Protection, P .O. Box 1, 3720 BA
Bilthoven, (2) Holland, MI, (3) Leiden, The Netherlands, (4) Ware, UK, (5) Belo
Horizonte, Brazil, (6) Geneva, Switzerland, (7) Bethesda, Md, (8), Frederick, Md, (9)
Darmstadt, PRG .
One of the interests of ICPEMC is to identify situations in which the possible
induction of inherited defects in man by mutagen exposure could actually be studied .
The large-scale use of mutagenic drugs in field programmes against Schistosomiasis,
mainly during the seventies, was considered a possible case . An ICPEMC task group
approached the problem by (1) updating the genetic toxicology data base for the
various antischistosomal drugs known, and (2) searching for possible study areas .
Expertise was combined from genetic toxicology, mutation epidemiology and tropical
medicine . It was considered that : (a) hycanthone is the best candidate drug, if any ;
(b) local demography would render the reliable tracking of substantial numbers of
offspring of treated persons an almost impossible task (c) in most endemic countries
proper diagnosis and registration of inherited defects is largely lacking ; (d) as
estimated from animal experiments the sample sizes needed to show an effect, if any,
would be very large; and (a) since non-mutagenic antischistosomal drugs are now in
use, the problem is of low priority in endemic countries that are usually short in
medical resources . Thus, studying offspring of hycanthone-trsated people to
demonstrate the mutagenic potential of the drug in manais not a viable enterprise .
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THE ROLE OF PROTEIN KINASE C IN SIGNAL TRANSDUCTION AND CELLULAR TRANSFORMATION . R.S .
Krauss, G .M . Housey . W .W.-L. Rsiao, M .D. Johnson, S .A. Rotenberg and I .B. Weinstein .
Comprehensive Cancer Center, Columbia University, New York, N .Y. 10032 .
We have utilized a retroviral expression vector to construct a series of rodent embryo
fibroblast cell lines that stably overexpress a full length cDNA encoding rat protein
kinase Cgj (PKC) . Rat 6(R6) cells that contain 20-53 fold higher PKC enzyme activity
than control cells show several disturbances in growth control, including the
ability to form small colonies in soft agar and tumors in nude mice . R6-PKC-3, a line
with a 53-fold increase in PKC activity, in hypersensitive to transformation by transfection
with an activated ras oncogene, as measured by the formation of large colonies
in soft agar . Recently, we have developed lines of C31i/10T1j cells that stably overproduce
PKC . 10Tk-PKC-4, a line with an 11-fold increase in PKC activity relative to control
cells (but with a specific PKC activity similiar to the R6-PKC lines), is morphologically
altered, grows to 4-fold higher saturation density and has reduced adhesiveness
. When grown in 2 .5% calf serum and 100 ng/ml TPA, these cells form numerous large,
dense foci . However, unlike the R6-PKC cell lines, neither 10TIS-PKC-4 calle nor calls
from the TPA-induced foci are capable of growth in soft agar, and they are non-tumorigenic
in nude mice . These R6 and 10711 cell lines should be useful for investigating
molecular events in tumor promotion and multistage carcinogenesis . We have also utilized
these cell lines as a source for obtaining enzyme preparations that are highly enriched
for PKCS1, thus facilitating biochemical analysis of this PKC isoform . The implications
of these studies with respect to the role of PKC in carcinogenesis will be
discussed . Supported by NIH grants CA02656 and CA08346 .
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REASSESSMENT OF SELECT NTP COMPOUNDS IN THE L5178Y/tk*/- MOUSE LYMPHOMA
ASSAY. R. Krehla and D . Clivea, aWellcome Research Laboratories, Research Triangle Park, NC
27709 USA
Strong conclusions have been drawn about the performance of 4 short term tests based on summary
(+, -) evaluations of the NTP-sponsored studies on 73 rodent carcinogens and noncarcinogens (Tennant
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