Study Set Content:
many spontaneous mutations are point mutations, a change in a single-base pair in the DNA sequence
MISMATCH REPAIR OF SINGLE-BASE MISPAIRS
DNA regions containing chemically modified bases, or DNA chemical adducts, are typically repaired by excision repair processes.
EXCISION REPAIR
The predominant mechanism or doublestranded DNA repair in multicellular organisms is nonhomologous repair, which involves the rejoining of the ends of the two DNA molecules.
END-JOINING REPAIR OF NONHOMOLOGOUS DNA
Ex. All mammalian cells possess apurinic endonucleases that unction to cut DNA near apurinic sites. The cut is then extended by exonucleases, and the resulting gap repaired by DNA polymerases and ligases
MISMATCH REPAIR OF SINGLE-BASE MISPAIRS
Ex. Proteins that slide along the surface of a double-stranded DNA molecule recognize irregularities in the shape of the double helix, and induce repair of the lesion.
EXCISION REPAIR
GENOTOXIC CARCINOGENS:
POLYAROMATIC HYDROCARBONS
Alkylating agents
Aromatic amines and amides
POLYAROMATIC HYDROCARBONS • Such as () are found at high levels in charcoal broiled foods, cigarette smoke, and in diesel exhaust
benzo(a)pyrene
Alkylating agents readily react with dna at more than () sites
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A class of chemicals with varied structures. Exposure to these chemicals was through the dye industry, although exposure still occurs through cigarette smoke and other environmental sources
AROMATIC AMINES AND AMIDES
INORGANIC CARCINOGENS: • Such as metals including
arsenic, beryllium, cadmium, chromium, nickel, and lead.
Direct-acting carcinogens
Nitrogen or sulfur mustards
Propane sulfone
Methyl methane sulfonate
Ethyleneimine
Indirect-acting carcinogens
Polycyclic aromatic hydrocarbons and heterocyclic aromatics
Aromatic amines
N-nitroamines
Azo dyes
Chemicals that function through this mechanism produce sustained cell death that is accompanied by persistent regenerative growth
NONGENOTOXIC CARCINOGENS
NONGENOTOXIC (EPIGENETIC) CARCINOGENS:
CYTOTOXICITY
RECEPTOR-MEDIATED
HORMONAL MODE OF ACTION
DNA METHYLATION AND CARCINOGENESIS
OXIDATIVE STRESS AND CHEMICAL CARCINOGENESIS
OXIDATIVE DNA DAMAGE AND CARCINOGENESIS
OXIDATIVE STRESS AND CELL GROWTH REGULATION
tumors by a nongenotoxic mechanism; organ specific
Phenobarbital-like Carcinogens
– activated Receptor-α (PPARα)
Peroxisome Proliferator –
Hormonally active chemicals include biogenic()()() hormones that cause tissuespecific changes through interaction with a receptor
amines, steroids, and peptide
are known to induce cell proliferation at their target organs.
Trophic hormones
– can induce tumors in estrogendependent tissue
Estrogenic agents –
induce neoplasia in the rodent thyroid.
Thyroid Hormone and TSH
