They directly damage DNA, but may or may not undergo metabolism to produce promutagens (metabolites that can have higher mutagenic potential than their substrates).
* Reactive oxygen species (ROS) – These may be superoxide, hydroxyl radicals and hydrogen peroxide, and large number of these highly reactive species are generated by normal cellular processes, for example as a by-products of mitochondrial electron transport, or lipid peroxidation. As an example of the latter, 15-hydroperoxyicosatetraenocic acid, a natural product of cellular cyclooxygenases and lipoxygenases, breaks down to form 4-hydroxy-2(E)-nonenal, 4-hydroperoxy-2(E)-nonenal, 4-oxo-2(E)-nonenal, and cis-4,5-epoxy-2(E)-decanal; these bifunctional electophils are mutagenic in mammalian cells and may contribute to the development and/or progression of human cancers (see 15-Hydroxyicosatetraenoic acid). A number of mutagens may also generate these ROS. These ROS may result in the production of many base adducts, as well as DNA strand breaks and crosslinks.
* Deaminating agents, for example nitrous acid which can cause transition mutations by converting cytosine to uracil.
* Polycyclic aromatic hydrocarbons (PAH), when activated to diol-epoxides can bind to DNA and form adducts.
* Alkylating agents such as ethylnitrosourea. The compounds transfer methyl or ethyl group to bases or the backbone phosphate groups. Guanine when alkylated may be mispaired with thymine. Some may cause DNA crosslinking and breakages. Nitrosamines are an important group of mutagens found in tobacco, and may also be formed in smoked meats and fish via the interaction of amines in food with nitrites added as preservatives. Other alkylating agents include mustard gas and vinyl chloride.
* Aromatic amines and amides have been associated with carcinogenesis since 1895 when German physician Ludwig Rehn observed high incidence of bladder cancer among workers in German synthetic aromatic amine dye industry. 2-Acetylaminofluorene, originally used as a pesticide but may also be found in cooked meat, may cause cancer of the bladder, liver, ear, intestine, thyroid and breast.
* Alkaloid from plants, such as those from Vinca species, may be converted by metabolic processes into the active mutagen or carcinogen.
* Bromine and some compounds that contain bromine in their chemical structure.
* Sodium azide, an azide salt that is a common reagent in organic synthesis and a component in many car airbag systems
* Psoralen combined with ultraviolet radiation causes DNA cross-linking and hence chromosome breakage.
* Benzene, an industrial solvent and precursor in the production of drugs, plastics, synthetic rubber and dyes.