Environmental and Molecular Mutagenesis - Legacy Tobacco ...

58 1989 EMS Abstracts
Notes injections (0, 25, 50, and 100 mg/kg) . Bone marrow smears were stained in acridine
orange (pH - 7 .4) and 2000 PCEs/souss were scored for NN-containing PCEs . The percent
PCEs was determined by counting 200 consecutive PCEs and normochromatics . Statistical
analyeas revealed that the three-treatment protocol vas superior . Therefore, this
protocol was selected by NIP for use in in vivo rodent bone marrow MN testing .
Additional experiments were done using this protocol to select a positive control dose
for both MMC and DNBA to be used in testing coded compounds . The positive control
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
doses chosen are 0 .2 mg l4lC/kg and 12 .5 mg DNSA/kg which lnduce about 8!Q4-PCEs/3000
PCEs . .[This research was supported by a contract fro's NTP, /NOI-ES-85208) .
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DEVELOPMENTAL AND GENETIC TOXICITY OF SHORT-CH4IN CARBOXYLIC ACIDS .
A . Esposito, G . Corsale, G .G . Giordano, and 0 . Pagano
Istituto Nazionale Tumori, 1-80131 Naples, Italy
The genetic and developmental toxicity of acidic pollutants was reported previously
(Pagano at al ., 1985a,b) ; a weak acid-induced teratogenic action was reported by Nau &
Scott (1986) on mammalian embryos, whereas the amidic analogues tested were ineffec-
tive on embryogenesis . A series of short-chain carboxylic acids (as sodium propionate,
malonate, and valproate), and their amidic analogues have been investigated for their
action on sea urchin (P .lividus) early development and fertilizatlon . Embryos were exposed
to acids (or amides) at levels ranging from 10-'M to 10-'M, without any detect-
able shift of medium pH ; the endpoint consisted of changes in the frequencies of :
a) developmental defects, and b) cytogenetic abnormalities . Sperm pretreatment experi-
ments led to the following outcomes : 1 . changes in fertilizstion success ; ii . alte :a-
tions of offspring quality, including mortality, developmental defects, and cytogenet-
ic abnormalities . The results showed that the acids exerted developmental toxicity at
levels ranging from 10-'to l0-°M, whereas their amidic analogues were ineffective up
to 10-= M . Cytogenetic analysis and offspring quality confirmed acid-induced genetic
damage, as reported previously . The data provide further evidence for the role of
acidic pollutants and drugs in affecting cell division and differentiation . (Supported
by the Italian Ministry of Health) .
(;ESiETIC REST FOR 7[PM P%WI'E17S ATID COCAACIIIO(04.S
Rudolf Fahrig, Department of Genetics, Frauntafer-Institut f(ir Tbotikologie ia ;d
Aerosolforschung, Ha:ne%rer 61, F .R. Gezmany
163
Escpariments with yeast and with mioe show that tumor prcmoters and cocarcinogens are
genetically active when given in eombinatien with a nutagen . The activity is indeperr
dent of the nutagen/carcinogen used but specific for a given eocarcinogen or tumor
praroter . 4fiere are striking similarities between the eacurrenoe of specific genetic
effects and specific effects in carcinogenicity tests :
1 . Cocarcinogens were ornutagenic .
2 . 2lanor promoters which are anticarcinogenic if given simultaneously with the carcinogen
were oorecaabinogenic and antinutagenio .
3 . Rtiamr promoters which can bA transforns+d into eocur.irwgcets reverted their genetic
effects fsrom corecambinogenicity to oortutagenicity upon metabolic activatien .
4 . Substances which are t:mor promoters as well as cocarcinogens were also comecaebinogens
and cenutagens .
The hypothesis presented offers plausible explanatiens for the meny divergent effects
of these substances in carcinogenicity tests . It therefare seems desirable to establish
the test procedure deacribed as stazt-tean tests for turor promoters and eocancisrogens
.
MULTIPLE ENOPOINT MJTATIONAL ANALYSIS IN TFE MOUSE
Jack Favor, GSF-Institut filr Slugetiergenetik, D-8042 Neuherberg, Germany, F .R .
164
Two main classes of mutational event from the wildtype allele are possible, loss
or gain type mutations . The type of mutational event is important in determining the
mutation rate observed and the effects of such mutant alleles when they occur in a
diploid, randomly mating population. A loss event represents the loss of functional
gene product . Such a mutation may result from a wide spectrum of DNA alterations
ranging from deletion to point mutation, and should have no phenotypic effect when
occurring as a heterozygote . A gain type mutational event represents an abnormally
functioning gene product, is likely due to a defective gene product or a misregulated
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