Hv. Malling et Rp. Weaver, MUTAGENESIS OF A SINGLE AT BASEPAIR IN MICE TRANSGENIC FOR PHIX174-AM3 PHIX174-CS70 - I - SPLEEN AND TESTIS, Mutation research. Genetic toxicology and environmental mutagenesis, 412(3), 1998, pp. 271-281
Mutations induced in a single AT base pair were studied in spleen and
testis by using mice transgenic for PhiX174 am3, cs70 and ethylnitroso
urea (ENU) as the mutagen. The transgenic mice were produced on the C5
7BL6/J background. The line (am54), which carries 50 copies of PhiX pe
r haploid genome integrated in a tandem array, was selected for experi
mental use and was maintained by random breeding. The animals for muta
genesis studies were produced by mating homozygous am54 males to wildt
ype C57BL6/J females. Hemizygous male offspring (8 to 10 weeks old) fr
om this cross were injected i.p. with 150 mg ENU per kg and were eutha
nized 3, 10 or 110 days after treatment. The spontaneous revertant fre
quency in the spleen was 1.42 x 10(-6) per plaque forming unit (pfu) a
nd in the testis it was 1.41 x 10(-6) per pfu. There was no significan
t difference between the two tissues. In spleen, it was not until 110
days after ENU treatment that the average revertant frequency among tr
eated animals was significantly higher than the revertant frequency am
ong the control animals. In spleen, the induced frequency of basepair
substitutions in the center AT basepair in the am3 nonsense codon was
2 x 10(-6). Also at this post-injection interval the variance of rever
tant frequencies in the spleen was not different from control variance
. In testis, the average revertant frequency 110 days post ENU injecti
on was not significantly different from the control. However, two impo
rtant observations were made regarding the testis data. First, one ani
mal had a significantly increased revertant frequency 110 days after E
NU treatment in comparison to the other four animals in the group that
had revertant frequencies equal to or lower than the average control
frequency. Second, the variance of revertant frequencies in the testis
among the treated animals increased as the post injection period incr
eased. Taken together, these observations may indicate that the revert
ants formed large clusters in one testis sample. (C) 1998 Elsevier Sci
ence B.V.