For large-scale genotoxicity screening in mam-

mals, metaphase analysis of bone marrow cells

is impractical. Searching for other end points
of chromosome damage in hematological prep-
arations from rodents, we demonstrated that
scoring micronuclei in young polychromatic
erythrocytes in bone , iarrow smears of mice
is a sensitive, simple, and reliable method. [The
SCI~indicates that this paper has been cited
in over 365 publications.]
Mutagenicity Testing Must
Be Practical
Werner S ch m id
Institute of Med ical Genetics
University of Zurich
CH-8001 Zurich
Switzerland
J une 26, 1990
Mutation research in Drosophila h ad b een
my early field of research between 1957 and
1961. A s an MD I th en turned to cytogenetics
and m ed ical genetics. In 1967, wh en claim s
were raised ab out m utagenic sid e effects of
ph arm aceuticals, m y h elp was sought, and for
th e next several years at the University of
Zurich I d evoted m uch of m y tim e not to
m utagenicity testing but first to working out
useful in vivo test system s. Togeth er with
G.R. S taiger, I b egan with ch rom osom e
analyses in th e b one m arrow of Ch inese h am -
sters. Despite a favorab le karyotype (2n =22),
such work was not acceptable for toxicological
screening. S ince we h ad observed th at treat-
m ents with classical m utagens caused severe
h em atological effects, I told K. Boiler,
2
a
m ed ical stud ent, to analyse h em atologically
stained b one m arrow smears.
Th e sh ift in proportions of d ifferent cell
types proved to be inconsistent and d ifficult
to quantitate. In contrast, a number of nuclear
anomalies showed a high degree of correlation
with th e results of our previous cytogenetical
studies. To simplify matters I decided to con-
centrate future studies on th e appearance of
m icronuclei in polychromatic erythrocytes.
Micronuclei as a consequence of m itotic ir-
regularities were, of course, known to cytol-
ogists since th e time of Boven. New, h owever,
was the subsequent demonstration that m icro-
nuclei in young erythrocytes, after expulsion
of th e m ain nucleus, were an extrem ely useful
feature apt forpractical toxicological screen-
ing. Whoever wants to promote a new method
sh ould d em onstrate its usefulness; th erefore
num erous basic methodological studies were
performed, of wh ich I wish to m ention only
two: B . Matter and 13 compared the test in six
m am m alian species and sh owed th at th e
lab oratory m ouse was h igh ly suitab le. Ten
model mutagens, not only clastogens, but
spind le poisons as well, were evaluated b y
P. Maier and me.
4
B efore directing m y research interests, in th e
m id -1970s, to oth er field s, I concentrated on
explaining and meticulously describing the
test. In th e b eginning, we m et with m uch
criticism and scepticism on th e part of cyto-
geneticists and m utation specialists b ut were
greeted with enth usiasm b y toxicologists who
finally saw a light in their difficult task. In other
circles, scepticism gave way to innum erab le
m od ifications and applications of scoring
micronuclel in all kind s of cell types and th eues,
includ ing human cells from precancerous and
cancerous lesions. In toxicology th e test was
successfully automated.~An overview of over
3 3 kinds of applications of micronuclei scoring
was pub lish ed in 1989.
, 1
CC/NUMBER 3 5
This Weeks Citation Classic a A UGUS T 27, 1990
Schmid W. The micronucleus test. Mutat. Res. 31:9-15. 1975.
[Division of Medical Genetics, Department ofPediatrics, University of Zurich, Switzerland]
I. Scbmid W&Stalger G R. Chromosome studies on bone marrow from Chinese hamsters treated with benzodiazepine
tranquillizers and cyclophosphamide. Muter. Res. 7:99-108, 1969. (Cited 140 times.)
2. Boiler K & Sdsmld W. Chemiache Mutagenese beim SSuger. Das Knochenmark des Chinesischea Hamsters als in vivo-
Testsystem. Hamatolologische Befunde each Behandlungmit Trenimon (Chemical mutagenesis in mammals. The bone
marrow of Chinese hamsters as an in vivo test system. Hematologicevidence after treatment with tremmon). Hum.
Genet. 11:35-54. 1970. (Cited 60 times.)
3. Matter B &Sdmsid W. Treuimon-istduced chromosomal damage in bone-marrow cells ofsix mammalian species, evaluated
by the micronucleus test. Muter. Rca. 12:417-25, 1971. (Cited 110 times.)
4. Mater P & Sdinild W. Ten model mutagens evaluatedby the micronucleus test. Muter. Res. 40:325-38, 1976.
(Cited 95 times.)
5. Romagna F &Staniforth C B. The automatedbone marrow micronucleus test. Murat. Rcs. 213:91-104, 1989.
6. Arlett C F, Aibby j. FIelder R J &Scott D. Micronuclei: origins, applications and methodologiesa workshop sponsored
by the Health and Safety Executive held in Manchester, May 23-25, 1988. Muragenesis 4:482-5. 1989.
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19~Ob y S I C U RRE N T C O N TE N TS