PMID- 12787914
OWN - NLM
STAT- MEDLINE
DCOM- 20030724
LR  - 20190702
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 527
IP  - 1-2
DP  - 2003 Jun 19
TI  - Effect of caloric restriction on Hprt lymphocyte mutation in aging rats.
PG  - 57-66
AB  - Caloric restriction (CR) reduces tumor incidence and retards aging in laboratory 
      animals, including non-human primates. Because of the relationships among 
      mutation, disease susceptibility, and aging, we investigated whether or not CR 
      affects the accumulation of somatic cell mutations in aging animals. Starting at 
      approximately 2 months of age, male CD rats (Harlan Sprague-Dawley-derived) were 
      placed on different levels of dietary intake: ad libitum (AL) feeding, and 90% 
      (10% CR), 75% (25% CR) and 60% (40% CR) of the total calories consumed by AL 
      animals. At 3, 6, 12, and 24 months after the beginning of CR, Hprt mutant 
      frequencies (MFs) were determined. The MFs measured in spleen lymphocytes from AL 
      and CR rats sacrificed at 3 months of dietary restriction were similar for all 
      dietary groups. However, the MFs at 6, 12, and 24 months of CR were significantly 
      higher in AL-fed rats compared with animals on 40% CR: (4.5+/-0.4)x10(-6) versus 
      (3.3+/-0.3)x10(-6) (P=0.032) in 6 months CR rats; (10.3+/-2.3)x10(-6) versus 
      (7.3+/-1.2)x10(-6) in 12 months CR rats (P=0.04), and (18.3+/-3.2)x10(-6) versus 
      (7.8+/-1.0)x10(-6) (P=0.001) in 24 months CR rats. In addition, rats receiving 
      25% CR for 24 months had a MF, (10.7+/-2.0)x10(-6), between the 40% CR and AL 
      rats. Multiplex PCR of the Hprt gene in mutant clones from 12 and 24 months 40% 
      CR rats and the corresponding AL rats detected deletions in 42% of CR mutants and 
      19% of AL mutants. Because of the difference in Hprt MF in the two groups, the 
      estimated MF associated with deletions in CR rats was similar to the deletion MF 
      in AL rats. This observation implies that the lower MF in CR rats is due to a 
      reduction in smaller Hprt mutations (i.e. base substitutions and frameshifts). 
      The pattern of smaller Hprt mutations from AL rats suggests that many were 
      produced by reactive oxygen species (ROS). The results indicate that CR reduces 
      the accumulation of spontaneous somatic cell mutation in aging rats, especially 
      those caused by base substitutions and frameshifts.
FAU - Aidoo, Anane
AU  - Aidoo A
AD  - U.S. FDA Jefferson Laboratories, Division of Genetic & Reproductive Toxicology, 
      National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, 
      USA. aaidoo@nctr.fda.gov
FAU - Mittelstaedt, Roberta A
AU  - Mittelstaedt RA
FAU - Bishop, Michelle E
AU  - Bishop ME
FAU - Lyn-Cook, Lascelles E
AU  - Lyn-Cook LE
FAU - Chen, Yi-Ju
AU  - Chen YJ
FAU - Duffy, Peter
AU  - Duffy P
FAU - Heflich, Robert H
AU  - Heflich RH
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - EC 2.4.2.8 (Hypoxanthine Phosphoribosyltransferase)
SB  - IM
MH  - Aging/*metabolism
MH  - Animals
MH  - Base Sequence
MH  - Cells, Cultured
MH  - *Energy Intake
MH  - Food Deprivation
MH  - Frameshift Mutation
MH  - Hypoxanthine Phosphoribosyltransferase/*genetics/metabolism
MH  - Lymphocytes/*enzymology
MH  - Male
MH  - Mutagenicity Tests
MH  - *Mutation
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Sequence Deletion
EDAT- 2003/06/06 05:00
MHDA- 2003/07/25 05:00
CRDT- 2003/06/06 05:00
PHST- 2003/06/06 05:00 [pubmed]
PHST- 2003/07/25 05:00 [medline]
PHST- 2003/06/06 05:00 [entrez]
AID - S0027510703000721 [pii]
AID - 10.1016/s0027-5107(03)00072-1 [doi]
PST - ppublish
SO  - Mutat Res. 2003 Jun 19;527(1-2):57-66. doi: 10.1016/s0027-5107(03)00072-1.