Mosaicism in female hybrid hares heterozygous for glucose-6-phosphate dehydrogenase. VI. Production of monotypism in the aortas of 4 of 10 mosaic hares fed cholesterol oxidation products.
The normal aortic tissue of black women heterozygous for glucose-6-phosphate dehydrogenase (G-6-PD) usually consists of two cell phenotypes (mosaicism). By electrophoresis two G-6-PD types are demonstrated (ditypism). Advanced atherosclerotic lesions from such women not infrequently yield samples displaying only one G-6-PD type (monotypism). Possible causes for the monotypism include (1) monoclonal origin of the lesion and (2) selective growth and/or survival advantage of one phenotype over the other. We have been attempting to produce monotypism in the aortas of a hybrid hare model that displays G-6-PD mosaicism in the normal state. In the current study 14 G-6-PD mosaic hares were fed a high-cholesterol diet for 6 to 17 months. All developed extensive moderately severe (as compared to humans) atherosclerotic lesions. No monotypic samples were found. Ten hares were fed (in addition to the standard high-cholesterol diet) small doses of one of two cholesterol oxidation products (25-hydroxycholesterol or triol) for 6 to 21 months. Four of the ten developed monotypic foci in either atherosclerotic lesions or normal aortic tissue or both. The reason for giving the oxidation products was because they are cytotoxic for cells in vitro and one (25-hydroxycholesterol) had been shown to be more toxic for one phenotype than the other with cultured fibroblasts from the mosaic hares (not infrequently resulting in the culture becoming monotypic). We suggest that the monotypism observed in vivo was probably produced by a mechanism similar to that operating in vitro.
D000818:Animals; D001011:Aorta / Q000201:enzymology* / Q000473:pathology; D001161:Arteriosclerosis / Q000201:enzymology / Q000473:pathology; D002777:Cholestanols / Q000494:pharmacology; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics*; D006579:Heterozygote; D006888:Hydroxycholesterols / Q000494:pharmacology; D009030:Mosaicism; D011817:Rabbits
D002777:Cholestanols; D002791:Cholesterol, Dietary; D006888:Hydroxycholesterols; C000474:cholestane-3,5,6-triol; C007997:25-hydroxycholesterol; D005954:Glucosephosphate Dehydrogenase