PMID- 8991059
OWN - NLM
STAT- MEDLINE
DCOM- 19970205
LR  - 20131121
IS  - 0893-6692 (Print)
IS  - 0893-6692 (Linking)
VI  - 28
IP  - 4
DP  - 1996
TI  - Temporal and molecular characteristics of lacZ mutations in somatic tissues of 
      transgenic mice.
PG  - 317-24
AB  - In order to help establish criteria for optimizing protocols for in vivo mutation 
      studies, lacZ transgenic mice (Muta mouse) were treated with five consecutive 
      daily doses of ethylnitrosourea (50 mg/kg), sampled at times up to 55 days after 
      treatment, and mutant frequencies and DNA sequences determined for liver and bone 
      marrow. In the bone marrow, the mutant frequency rose very rapidly in the first 5 
      days after treatment to 34 times the control frequency. Subsequently, there was a 
      brood peak where the mutant frequency did not vary significantly, although it did 
      appear to begin to decline after 45 days. In contrast, in the liver, the peak 
      mutant frequency (11 times the control frequency) was not achieved until 35 days, 
      after which there appeared to be a slow decline up to 55 days, which was not 
      statistically significant. Once the maximum mutant frequency was reached, the 
      mutation spectra in the two tissues were indistinguishable. In contrast to the 
      G:C-->A:T transitions in 5'-CpG sites characteristic of untreated mice, A:T-->T:A 
      transversions and A:T-->G:C transitions were prominent in both liver and bone 
      marrow of ENU-treated mice, suggesting the involvement of unrepaired O2- and 
      O4-ethylthymine adducts. In addition, G:C-->T:A transversions were induced in 
      liver. This study demonstrates the possibility that although tissues may have 
      different mutation fixation times, a single mutation fixation time equal to the 
      longest time may be appropriate for in vivo mutation studies, provided that the 
      mutation frequency does not decline appreciably after the peak is reached. This 
      study also illustrates the necessity of ensuring that mutation characteristics 
      are determined after optimal fixation has occurred.
FAU - Douglas, G R
AU  - Douglas GR
AD  - Mutagenesis Section, Health Canada, Ottawa, Ontario, Canada.
FAU - Jiao, J
AU  - Jiao J
FAU - Gingerich, J D
AU  - Gingerich JD
FAU - Soper, L M
AU  - Soper LM
FAU - Gossen, J A
AU  - Gossen JA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Environ Mol Mutagen
JT  - Environmental and molecular mutagenesis
JID - 8800109
RN  - 0 (Mutagens)
RN  - EC 3.2.1.23 (beta-Galactosidase)
RN  - P8M1T4190R (Ethylnitrosourea)
SB  - IM
MH  - Animals
MH  - Bone Marrow/*drug effects
MH  - Ethylnitrosourea/toxicity
MH  - Liver/*drug effects
MH  - Mice
MH  - Mice, Transgenic/*genetics
MH  - Mutagenicity Tests/methods
MH  - Mutagens/toxicity
MH  - *Mutation
MH  - Sequence Analysis, DNA
MH  - Time Factors
MH  - Tissue Fixation/methods
MH  - beta-Galactosidase/drug effects/*genetics
EDAT- 1996/01/01 00:00
MHDA- 2000/06/20 09:00
CRDT- 1996/01/01 00:00
PHST- 1996/01/01 00:00 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1996/01/01 00:00 [entrez]
AID - 10.1002/(SICI)1098-2280(1996)28:4<317::AID-EM4>3.0.CO;2-8 [pii]
AID - 10.1002/(SICI)1098-2280(1996)28:4<317::AID-EM4>3.0.CO;2-8 [doi]
PST - ppublish
SO  - Environ Mol Mutagen. 1996;28(4):317-24. doi: 
      10.1002/(SICI)1098-2280(1996)28:4<317::AID-EM4>3.0.CO;2-8.