Plaque-type mutations

Double-stranded DNA of SPPi was treated with hydroxylamine or nitrous acid to induce mutations. The biological activity of such DNA decreases with such treatment concomitant with an increase in the frequency of plaque-type mutations. When separated strands of SPPi were subjected to the same treatment and later reanneaUed with nonmutagenized complementary wild-type strands, different rates of inactivation as well as of occurrence of mutants were found for the two strands (Spatz and Trautner, 1970). 

Mutations Much of our knowledge of viral reproduction and how it is regulated has depended on the isolation and characterization of virus mutants. Several kinds of mutants have been studied in viruses host-range mutants, plaque-type mutants, temperature-sensitive mutants, nonsense mutants, transposons, and inversions. 

Mutation has been essential to Mendelism at every step, not only as the source of heritable variations-round peas or wrinkled, vermillion eyes or the wild type, rough plaque or smooth-but as a tool for understanding. -Horace Freeland Judson, The Eighth Day of Creation... 

Of the many disorders of lipoprotein metabolism (Tables 5.2 and 5.3), familial hypercholesterolaemia type II may be the most prevalent in the general population. It is an autosomal dominant disorder that results from mutations affecting the structure and function of the ceU-surface receptor that binds plasma LDLs and removes them from the circulation. The defects in LDL-receptor interaction result in lifelong elevation of LDL cholesterol in the blood. The resultant hypercholesterolaemia leads to premature coronary artery disease and atherosclerotic plaque formation. Familial hypercholesterolaemia was the first inherited disorder recognised as being a cause of myocardial infarction (heart attack). 

There are obviously some similarities between the development of fibrotic tissue in silicotic lungs and the development of atherosclerotic plaques in arteries. In both cases there is loss of elasticity and abnormal proliferation of one type of tissue. Also there is development of necrotic tissue. As pointed out by Benditt (296) the plaques were previously thought to consist of fibroblasts but have now been identified as smooth muscle cells. The growth of the plaque appears to involve a mutation that leads to proliferation of smooth muscle cells which thicken the artery wall and lead to necrosis within the plaque mass. Benditt cites possible agents of mutation as chemical mutagens, viruses, and ionizing radiations. 

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