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Adenine

Deamination In addition to its spontaneous occurrence (see Figure 17.17), deamination can be induced by some chemicals. For instance, nitrous acid deaminates cytosine, creating uracil, which in the next round of replication pairs with adenine (see Figure 17.20b), producing a C-G:T-A transition mutation. Nitrous acid changes adenine into hypoxanthine, which pairs with cytosine, leading to a T-A:C-G transition. Nitrous acid also deaminates gua-nine, producing xanthine, which pairs with cytosine just as guanine does; however xanthine may also pair with thymine, leading to a C-G:T-A transition. Nitrous acid produces exclusively transition mutations and, because both C-G:T-A and T-A:C-G transitions are produced, these mutations can be reversed with nitrous acid.

Hydroxylamine Hydroxylamine is a very specific base-modifying mutagen that adds a hydroxyl group to cytosine, converting it into hydroxylaminocytosine (see Figure 17.20c). This conversion increases the frequency of a rare tautomer that pairs with adenine instead of guanine and leads to C-G:T-A transitions. Because hydroxylamine acts only on cytosine, it will not generate T-A:C-G transitions; thus, hydroxylamine will not reverse the mutations that it produces.

Oxidative reactions Reactive forms of oxygen (including superoxide radicals, hydrogen peroxide, and hydroxyl radicals) are produced in the course of normal aerobic metabolism, as well as by radiation, ozone, peroxides, and certain drugs. These reactive forms of oxygen damage DNA and induce mutations by bringing about chemical changes to DNA. For example, oxidation converts guanine into 8-oxy-7,8-dihydrodeoxyguanine (Figure 17.21), which frequently mispairs with adenine instead of cytosine, causing a G-C: T-A transversion mutation.

Intercalating agents Intercalating agents, such as pro-flavin, acridine orange, ethidium bromide, and dioxin are

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