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Effect of transgene number of spontaneous and radiation-induced micronuclei in lacl transgenic mice

Journal Article · · Environmental and Molecular Mutagenesis
OSTI ID:88905
; ; ;  [1];  [2]
  1. SRI International, Menlo Park, CA (United States)
  2. Stratagene, La Jolla, CA (United States)

Lacl transgenic mice are widely used for the measurement of mutations in specific target issues. The lacl transgene is present in mice as 40 tandem repeats; this sequence is homozygous (contained in both copies of chromosome 5) in C57Bl/6 mice, and is hemizygous in B6C3F1 mice. Previous reports have indicated that tandem repeats can produce chromosome instability, fragile sites, and other effects. To determine whether the presence of the transgene effects micronucleus induction we compared the response of nontransgenic (NTR) to hemizygous (HEMI) transgenic B6C3F1 mice and to hemizygous and homozygous (HOMO) transgenic C57Bl/6 mice. Five mice/group were irradiated with 500 cGy from a {sup 137}Cs source. Bone marrow was harvested 24 hr after treatment and 2000 polychromatic erythrocytes (PCE) were analyzed per animal. The presence or absence of the lacl transgene had no effect in unirradiated mice on the percent of micronucleated PCE (MN) or on the ratio of PCE to total red blood cells for either strain: B6C3F1 mice had MN frequencies of 0.26% and 0.20% for NTR and HEMI mice, respectively; C57Bl/6 mice had MN frequencies of 0.34%, 0.32%, and 0.38% for NTR, HEMI, and HOMO mice, respectively. Radiation-induced micronucleus frequencies were significantly higher in HEMI lacl B6C3F1 mice (2.85%) than in NTR litter mates (1.59%); the converse was true in C57Bl/6 mice: NTR were 2.45%, HEMI were 1.25%, HOMO were 1.65%. These data suggest that the lacl transgene does not cause chromosome instability as measured by spontaneous micronucleus levels. However, the response of these transgenic mice to a variety of clastogenic agents needs to be investigated before they are integrated into standard in vivo assays for chromosome damage.

OSTI ID:
88905
Report Number(s):
CONF-9405324--
Journal Information:
Environmental and Molecular Mutagenesis, Journal Name: Environmental and Molecular Mutagenesis Journal Issue: Suppl.23 Vol. 23; ISSN 0893-6692; ISSN EMMUEG
Country of Publication:
United States
Language:
English

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