Environmental and Molecular Mutagenesis - Legacy Tobacco ...

212 1989 EMS Abstract s
Notes -fn the devel.ofle>srtf6t only of human cancer but also of other disorders, including
neural diseaser
Phenol and initle derivatives were identified as nitrosatable mutaRen precursors
in soybean fer16et4rat7e'n products and vegetables . Broiled meat and fish also contained
nitrosatable precursors . Pher.olic derivatives reacted with nitrite to produce
mutagenic diazo compounds . 3-Diazotyramine formed from tyramine and nitrite was
carcinogenic to rate . In the case of indoles . N-1 and/or C-3 nitrosated compounds
were formed . 1-Nitrosoindole-3-acetonitrile formed DNA adducts in both the forestomach
and glandular stomach of rats . A carcinogenicity teat of this ritrosoindole is
ongoing .
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
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DIFFERENCE BETWEEN INTRAPERITONEAL AND ORAL GAVAGE APPLICATION IN THE MICRONUCLEUS TEST
The Collaborative Study Group for the Micronucleus Test, CSGMT/JEMS-MMS, Organizers : A .
Wakata(Yamanouchi Pharm . Co., Ltd . . Tokyo) N . Hayashi(Natl . Inst . Hygienic Sci . .Tokyo),
S. Sutou(Itoham Foods Inc ., Tokyo), H. Shimada(Daiichi Seiyaku Co ., Ltd., Tokyo) . S.Sato
(Japan Tobacco Inc ., Kanagaea), and Y .F. Sasaki(lnst . of Env . Toxicol . . Tokyo)
As a collaborative study of CSGMT/JEMS MMS by 34 participating organizations, the ip
and po administration routes were compared using 2 mouse strains . MS/Ae and CD-1 . and 17
chemicals with various modes of action (Ara-C . 6-MP, B[ajP . DMBA . 2AAF . Phenacetin . CYP.
EMS . ENU . MMS . MMC, COL . VINC, KBrO3, KrCrO„ Benzene and PCZ). On the basis of the
findings of an acute toxicity and a pilot experiment for dose and sampling time, a full
scale experiments were performed on each chemical . Almost all chemicals shored a
positive response in ■icronucleus induction by both routes of administration in both
mouse strains . Contradictory outcomes were obtained between the ip and po routes on
potassium chromate in both strains (ip :positive, po :negative) . In the CD-1 ■ice, benzene
remarkably induced ■icronuclei when administered po, but gave only a marginal response
when administered ip . Generally the chemicals induced ■icronuclei at lower dose levels
(mg/kg) by the ip route . This tendency, hotever, was decreased or even reversed when
dose was expressed as percentage of the LD$ . . Although the ip route, an artificial
exposure route, is useful to detect the inducibility of ■icronuclei of test chemical per
se at a small dose, the po route seems sensitive and valuable enough to evaluate the
test chemicals . When the dose levels of chemicals are adjusted on the basis of the
LD, ., both routes are acceptable as routes of administration in the ■icronucleus test .
CHARACTLRIZATION OF METABOLITES OF
2-AMINO-3,8 DIMETHYL-IMIDAZO(4,S-f)QUINOXALINE .
HlYsa Wallin, lera A. Holme, Oeorg Becher and Jan Alexander.
Department of Toxiwlogy, National Institute of Public Health,
N-0462 Oslo Norway.
2-Amino-3,8-dimethylimidaxo(4,5-J)quinoxaline was metabolized by Isolated liver
celle from PCB treated rata to at least 10 metabolites . The five major metabolites
which were also major metabolites excreted from the rat were etructuraily determined .
Three of the metabolites contained sulfate, on evidence of the Incorporation of
radioactive sulphur and the requirement of tultotraasferase for their fotmation .
Chemical synthesis, NMR, UV and mast tpeciroseopy revealed that the major
metabolite was 4 or S-MeIQx-sulfate (formed from 4 or S-hydroxy-MeIQx) . The
other two were MeIQz=2-sulfamate and 8-hydroxymethyl-MdQx-S-sulfate. Two of
the metabolitea displayed the protons from a glucuronie acid group . The were
ideatified 4 or S-O-glucoaiduriayl-MeIQx (formed from 4 or S-hydroxy-MeIQx) and
N-gWcosidurlnyl-MeIQx. We also obtained evidence for the formation of a glutathione
conjugate .
ELIfA FOR FOOD MUTAGEN S
Hlkaa Willis, Karis:,6rEpltierj, 014 Jerges Roulaad, Otorj Becher and Jaa Akxaader .
Depfrtmest of Toxisology, Natioaal Ieetitnte of Public Health ,
N-0462 Oab Norway .
To aeseu the risk !oVamiaqimldazo =,azaareaee (AIA) to human popelatiow it Is aeatuery to
know more about the kveL of t>,eee compounds Is common foods . We'beHeve that immssoawys
♦dll provide both the ipeoificity and the sensitivity seeded for this task and may be rnn Is
larae seriet with relative little work effort .
Our object was to develop its t?LISA for several different AIA. We therefors prepated astigeas
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