Genetic variation in the response of mice to xenobiotics in vitro. I. General methodology and response to some model compounds.
A new method for studying genetic variation in the response of laboratory mice to xenobiotics using in vitro cultures of somatic cells has been developed. When resident peritoneal cells from ten mouse strains were cultured with methanol, ethanol, dimethylsulphoxide, sodium butyrate, aspirin or trypan blue, each at two dose levels, significant strain differences in response (total protein) were noted for each xenobiotic except methanol, showing that responses are under genetic control. Strain differences in final protein (growth) were also noted. The two alcohols were least toxic, but aspirin was most toxic to strains with fast-growing cells. Most strain means had a gaussian distribution suggesting polygenic control. However a non-gaussian distribution, possibly due to a single dominant resistance gene in C57BL/6 mice, was seen with the 0.6 mm-butyrate. Differential strain responses to various alternatives to foetal bovine serum were also noted. In another study involving 19 mouse strains, the five strains with the Coh(h) or Coh(i) (strain CBA) genotype ranked 1, 2, 3, 4 and 6 in sensitivity to 2.5 mm-coumarin (P < 0.001) and were significantly more sensitive (49.2 +/- 5.9% of controls) than the 13 strains known to have the Coh(l) genotype (65.0 +/- 8.8% of controls). This economical and humane in vitro method may provide a useful new tool for studying the genetics of response to xenobiotics at the cellular level.
Festing
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MRC Experimental Embryology and Teratology Unit, Carshalton, Surrey SM5 4EF, England.
Eydmann
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