Strain differences in haematological response to chloroamphenicol succinate in mice: implications for toxicological research

Much toxicological research continues to be done using genetically undefine d "outbred" stocks of mice and rats, although the case for using isogenic s trains has been made repeatedly in the literature over a period of more tha n two decades. Also, very few studies are conducted using more than one str ain, with the result that genetic variation in response is seldom apparent to the investigator. Here we report qualitative and quantitative strain dif ferences in the haematological response to chloramphenicol succinate (CAPS) when administered by gavage at 500-2500 mg/kg for 7 days, to four inbred s trains 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 fo ur inbred strains showed significant (P <0.01) responses to CAPS at lower d ose 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 sen sitive experiment than the use of 47 CD-1 mice alone, and would also have s hown that the response is partly strain dependent. These studies provide ad ditional evidence that inbred strains, because of their greater sensitivity and other valuable properties, should be more widely used in toxicology. ( C) 2001 Elsevier Science Ltd. All rights reserved.