CHEMICAL MUTAGENS

Presented by
Nargis Ammarah Jameela Aneela Azra

PROPOSED BY DR. SADAF TABASUM

MUTAGEN TYPES OF MUTAGENS MOLECULAR MECHANISIM INVOLVED IN CHEMICAL MUTAGENS

HYDROXYLAMINES BASE ANALOGS ALKYLATING AGENTS DNA INTERCALATING AGENTS OXIDATIVE DAMAGE

A mutagen is any chemical or radiation that cause change in nucleotide sequence (Nitrogen base) in genomic (DNA/RNA)

Chemical mutagen: Chemical mutation of chemical compounds that cause mutation in DNA or chromosomes.

Physical mutagen: Physical mutagen that caused by physical factor such as: Radiation UV radiation and ionizing radiation

It is an inorganic compound used to introduce Random mutations by switching base pairs from A to G, or from C to T by deaminating bases. Hydroxylamine(NH2OH) reacts with pyrimidine bases. Its effect is strong on cytosine while on uracil the effect is less. Hydroxylamine breaks and removes pyrimidine ring of uracil thus producing phosphribosyl urea and 5 isoxasolone with cytosine, hydroxylamine finaly produces hydrxyl amino (-NOH) derivative, which might be responsible for base pair change (GC-AT pair)

Base analogs have a structural similarity with the normal bases so that they are metabolized and incorporated in to DNA during replication, but they increase the frequency of mis-pairing and thus cause mutation. These agent only mutate replicating DNA. e.g. The most commmonly used base analog is 5 bromouracil (Brdu) base analog derived from thymine. It under go slight change in its structure called a tautomaric shift to which case it to base pair with guanine. After replication AT base pair is replicated by GC on one of the daughter to a point mutation.

These agents carry one, two or more alkyl groups in reactive form, thus modifyDNA base sequences by the transfer of methyl or ethyl group such that their base-pairing alterd from GC to AT. These intefere with DNA replication and transcription leading to mutation. Alkylating agents may cause cross-linking of DNA and thus cause lethal effect by inhibting DNA replication. Alkylating agents may also react with PO4 group and may the sugar phosphate backbone of DNA that result in chromosomes breaks and gross mutation .

A chemical that can insert itself b/w the bases in the DNA double helix, possibly causing a frameshift mutation. They interfere with transcription, replication and induce mutation. (e.g ethidium bromide). Ethidium bromide pushes adjacent base pairs to move a part slightly as a result reading frame is shifted.

Nitrous acid converts amine group on A and C to diazo groups, altering their hydrogen bonding patterns which leads to incorrect base pairing during replication.