Environmental and Molecular Mutagenesis - Legacy Tobacco ...

283 1989 EMS Abstracts 99
SPECIES COMPARISONS REGARDING COMPARATIVE METABOLISM OF TWO STRUCTURALLY SIMILAR Notes
NITROPHENYLENEDIAMINES (HC BLUE 1 AND HC BLUE 2) . F . Kari, S . Driscoll, C . Parker,
K . Rudo, K . Tomer, and R . Langenbach ; National Inst u e of Environmental Health
Sciences, Research Triangle Park, NC 27709 . Chronic evaluations reveal that HC Blue
1 causes hepatocellular carcinomas in mice, but a structural analog, HC Blue 2 is not
carcinogenic in mice . Neither of these chemicals are carcinogenic in rats . The
bioassay results of this carcinogen/non-carcinogen pair mirror the species- and
organ- specificity obtained with 23 congeners which have been evaluated under
similar conditions . Accordingly, comparative metabolism studies were done to elucidate
mechanisms for their discordant carcinogenic potencies and species-specificity .
Urinary recovery of radiolabel following oral administration of the parent compounds
was equivalent for both compounds in mice and rats . Conversion of parent compounds
to metabolites was quantitatively comparable indicating systemic availability is not
responsible for the discordant potencies . Metabolism of these two compounds (200pM)
by hepatocytes isolated from mice and rats yields metabolic profiles similar to their
respective in vivo profiles . HPLC separation shows that in mice HC Blue 1 Is metabolized
to five major metabolites while the non-carcinogen HC Blue 2 yields only one
major metabolite . Thermospray LC/MS analysis of HC Blue 1 metabolites from mice provides
tentative evidence for nitroreduction, demethylation and conjugation
(acetylation and glucuronidatton) . In the non-susceptible rat, HC Blue 1 produces
three metabolites similar to those found in mice, but two metabolites produced in
mice are notably decreased or absent in rats . Qualitative differences in metabolism
of these compounds may contribute to their different carcinogenic potencies and
species specificity .
284
INDUCTION OF CHROMOSOME-TYPE ABERRATION AT ZYGOTE FOLLOWING CHLORAMBUCIL ADMINISTRATION
IN MALE MICE, M .Katoh and R .P .A .Valdivia, Food and Drug Safety Center, Hadano,
Kanagawa (JAPAN), and University of Chile, Santiago (CHILE)
Katoh et al . (1986) reported that most alkylating chemicals which are shown dominant
lethals in postmeiotic male germ cells induce chromosome-type aberrations at zygotes
and these agents associated with the inductions of heritable tranalocations~in offspring
. Chlorambucll, which is an alkylating agent of the nitrogen mustard type,
induced the high frequencies of dominant lethals in male germ cells except late spermstids
(personal communication by W .M .Generoso) . This dominant lethal's pattern is the
complete opposite of that observed by acrylamide which 7bhoved sperm protamina alkylation
but not of DNA alkylation (Shelby et al .1986, Saga et a1 .1988) . Also, cytogenetic
analyses by acrylamide demonstrated chromosome-type aberration (this result
is presented by R .P .A .Valdivia in FIFTH ICEM 1989) . In the present study, cytogenetic
analyses by chlorambucil were undertaken to clarify the mechanisms for chromosome
aberrations in male germ cells of mice . Male mice were given single intraperitoneal
injections of 25, 12 and 6 mg/kg of chlorambucil and then cytogenetic analyses at
zygotes were carried out for 5 weeks after injection . The frequency pattern of zygotes
with chromosome aberrations was found to correlate with that of dominant lethal . The
sensitive germ cell stages were demonstrated in late spermatocytas, early .permatids
and late spermatozoa . Late spermatid stage was ruled out . In these sensitive stages,
chlorambucil induced chromosome-type aberrations . These evidences show that the induction
mechanisms of chromosome-type aberration by chlorambucil is different from that
of sperm protamine alkylating agents such as acrylamide and methyl methanesulfonate .
285
MUTAGENICITY TEST FOR GASEOUS AND VAPOUROUS COMPONENT OF COMBUSTION EXHAUST . A .Kawai',
S .Goto', O .Endo', H .Matsushita=, 'Japan Automobile Research Institute, Tsukuba,
Ibaraki,(Japan), 'National Institute of Public Health, Minato-ku,Tokyo (Japan) .
Many reports have been published for the sutagenicity of particulate component of various
combustion exhausts, but few for the mutagenicity of gas/vapour cosponent of these exhausts .
We devised apparatus for sutagenicity assay of gas/vapour co.pounds and obtained a suitable
test condition for this assay . Particle-free test gas was prepared by passing a diluted
combustion exhaust through quartz fibre or similar filter, collected in a Tedra bag (200 l),
and diluted with fresh air . The test gas was introduced into a Pyrex glass chasber(3 or 8 L)
in which 10 or 16 test plates having tester strain on the surface were placed inversely .
Following test condition was selected fros various kinds of test results as a suitable one
for autagenicity assay ; 0 .251 /ein for flow rate of test gas, 2-8 hr for exposure time, and 37
'C for the temperature of chamber . Mutagenicity test was carried out for the particle-tree
exhaust gas from diesel engine,kerosene heator and side-streas of cigarette smoking,using
Salmonella typhisurius TA98 and TA100 . E .Coli WP2uvrA/pKM101 was also used for the test of
cigarette smoke . Gas/vapour component of diesel exhaust gave positive sutagenic responses for
TA100 with and without S9 ∎ix and for TA98 with 39 six . The component of kerosene heater
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