Chemical and physical mutagens can cause mutations by replacing one
base with another in the DNA molecule, causing structural changes in a
base so that it causes it to mispair, causing insertions or deletions, or damaging
a base so much that it is unable to pair with any other normal base.
Base analogs are sufficiently similar to the normal nitrogenous bases in
DNA that they can be incorporated into a replicating DNA molecule by
DNA polymerases. Once incorporated, however, base analogs have abnormal
base-pairing properties so that they produce mutations during
subsequent DNA replication cycles. For example, 5-bromouracil and 2-
amino-purine are two common base analogs.
Alkylating agents cause mutations by chemically altering bases so
that they pair up with a specific base other than the normally complementary
base. Intercalating agents are planar molecules that can insert
themselves between the stacked bases within the double helix. These
agents alter the molecule of DNA in such a way that DNA polymerases
may insert or skip one or more bases during replication, often resulting
in frameshift mutations. For example, proflavin, acridine orange, and
ethidium bromide are intercalators.
When ultraviolet light is absorbed by adjacent pyrimidines in one
strand of a DNA molecule, a dimer forms. These dimers interfere with
proper base pairing during DNA replication. The impact is so extensive
that the normal replicative process is stopped until these dimers are repaired.