Environmental and Molecular Mutagenesis - Legacy Tobacco ...

172 1989 EMS Abstracts
Notes '" rULTRA-VIOLET-.1NDUCED MUTATION SPECTRA ON SIMIAN VIRUS 40 GENES AFTER DNA
TRANSFECTION OR VIRUS INFECTION .
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
A. SARASIN,. Az■LtOftENBEROER and F. BOURRE.
498
Laboratory of Molecular Genetics, Institut de Recherches Scientifiques our Is Cancer, B .P. n° 8, 94802 -
VILLEJUIF (France) .
The analysis of induced mutations In mammalian cells has become a major goal for the understanding of
the carcinogenesis Initiation . Due to the complexity of the cNlular genome, the use of small and easily
manipulatable DNA probes, depending on cellular enzymic machinery, is highly desirable . Two such systems
have been developed : shuttle vectors and animal virus mutants . We have used the latter one with either natural
SV40 or modified SV40.
Simian virus 40 (SV40) has been used after being treated In vitro with ultraviolet light (UV) . Our
mutation assay is based upon the reversion of a temperature-sensitive (ts) growth at 411C to a wild-type
growth phenotype. UV Irradiation of is 8V40 DNA leads to the Induction of temperaturalndependent phenotypic
revenants which are due to singie-base substitutions located opposite potential UV-Induced DNA lesions . This
mutagenesis appears therefore to be targeted opposite lesions . Treatment of UV-irradiated DNA with the E . coli
photolyase increased virus survival and strongly decreased virus mutagenesis . The mutation spectrum is
different after photoreactivatfon implying that pyrimidine dimers and Py(8-4)Py photoproducts are both
premutagenic lesions .
UV-irradiated or unirradiated SV40 virions or SV40 naked DNA have been used with the same
phenotypic reversion assay . It appeared that the transfection step, used with naked DNA, and the Infection lead
to different results for mutagenesis . Indeed the UV-tnduced mutation spectra were similar but not Identical
while the spontaneous mutation spectra were different regarding the location of mutation hot spots .
GERMINAL IMPRINTING IN CHROMOSOME MUTATION
M. S. Sasakl, Radiation Biology Center, Kyoto University, Kyoto (Japan )
499
There is now a growing body of evidence indicating that the non-Robertsonlan de vo
chromosome mutations have a strong bias toward paternal origin . Such non-randomness has
been implicated as a reflection of differential susceptibility to errors in meiotic process
between males and females. However, we meet some difficulties with this idea . Deletion
or loss-of-function mutation of retinoblastoma susceptibility (RB) gene has a critical role in
the development of retinoblastoma and also presumably Dsteosarcoma . Investigation on the
parental origin of de novo chromosome mutations involving- RB gene In retinoblastoma
patients showed that the germinal mutations were predominantly paternal origin, providing
an additional evidence for the paternal melotic errors. In the non-hereditary sporadic
osteosarcoma, the Initial mutation is presumed to be somatic origin . The mutation of
tumor auppressing gene is often expressed by a subsequent loss of a large piece, or all, of
the chromosome which harbors the normal allele. When the parental origin of chromosomes
was identified with polymorphic loci, 12 out of 13 tumors showed loss of maternally
derived chromosome 13 alleles, indicating that the Inltial somatic mutations were also
non-random and occurred predominantly on paternally derived chromosome 13 . The
preferential Involvement of paternal chromosomes both in germinal and somatic mutations
rather suggests the involvement of germinal imprinting In the mutational susceptibility .
500
CYMIAGICAL ACfIVTTY OF NATURALLY OOCURRING 1K)GS --- S7UDIFS CN PFRILIA EICIRACPS
Mieko Sasaki, 4bkyo Metr.Res.Iab .P,H.,3-24-1 Hyakunin-cho,Shinjuku-ku,7bkyo 169,Japan
Naturally occurring substances have been widely used as drugs and food additives .
Toxicology of these substances, however, is not studied enough because aLnost all of
them are carplex chemicals and their activities are difficult to be examined . On the
other hand, anti-mutagenicity or anti-wrcinogenicity has been found in some of these
materials. Recently, Chinese medicine (naturally occurring drugs) has been interested
and considered again in Japan, as a therapy for canoer or chronic diseases . The
effects of these drugs have not been established enough yet, and the qualitative and
quantitative studies bacome necessary now .
Perillae (leaf of Perilla frutescens var.acuta) is one of popular herbs in Japan,
and has been used as a food for expecting a good smell and anti-spoiled effect, and
it is mixed into the Chinese medicine for armron cold concerning In its anti-allergic
effect. The main active earnponent of perillae is known as perillaldehyde, and
another toxic derivative, perilla ketone, is a potent puLronary edematogenic agent
in farm animals. Biological activity of the ether-, ethanol-, water-extracts from
leaves of perilla and purified 1-perillaldehyde was investigated in cultured CAD-K1
cells. Chemical analysis of these samples was practiced by capillary OC or HPLC .
Aberratiens of chratnsone were increased in cells treated with the ether-extract ,
and weak mutagenicity was also observed. The correlation of cytological activities
to chemical analysis has been exadlLned, and the other biological effect, such as an
effect on inaraua-earpetent cells, has been studied to estimate the Chinese medicine .
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