Strain differences in haematological response to chloramphenicol succinate in mice: implications for toxicological research.
Much toxicological research continues to be done using genetically undefined "outbred" stocks of mice and rats, although the case for using isogenic strains has been made repeatedly in the literature over a period of more than two decades. Also, very few studies are conducted using more than one strain, with the result that genetic variation in response is seldom apparent to the investigator. Here we report qualitative and quantitative strain differences in the haematological response to chloramphenicol succinate (CAPS) when administered by gavage at 500-2500 mg/kg for 7 days, to four inbred strains of mouse (C3H/He, CBA/Ca, BALB/c and C57BL/6) and one outbred stock (CD-1). CAPS caused anaemia and reticulocytopenia in all mouse strains, and leucopenia in the inbred strains but not in the outbred CD-1 stock. All four inbred strains showed significant (P<0.01) responses to CAPS at lower dose levels than in CD-1 mice, which were phenotypically more variable than the inbred animals. A simulated experiment, using a sample of records from the present study, showed that the use of two mice at each dose level using CD-1, CBA, BALB/c and C57BL/6 (48 total mice), would have given a more sensitive experiment than the use of 47 CD-1 mice alone, and would also have shown that the response is partly strain dependent. These studies provide additional evidence that inbred strains, because of their greater sensitivity and other valuable properties, should be more widely used in toxicology.
Festing
M F
MF
MRC Toxicology Unit, Hodgkin Building, University of Leicester, PO Box 138, Lancaster Road, LE1 9HN, Leicester, UK. mfwf1@leicester.ac.uk
Diamanti
P
P
Turton
J A
JA
D000704:Analysis of Variance; D000741:Anemia, Aplastic / Q000139:chemically induced* / Q000235:genetics; D000818:Animals; D001773:Blood Cells / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001947:Breeding; D002701:Chloramphenicol / Q000031:analogs & derivatives* / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D014644:Genetic Variation / Q000187:drug effects; D005838:Genotype; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype
D002701:Chloramphenicol; C026016:chloramphenicol succinate