DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity

Cyclone damage along Lee Point Road

Cyclone damage along Lee Point Road, view from McMillans Road end. Shows houses along street, water tower prominent on right.Unknown

Destruction caused by Cyclone Tracy in Moil

Some of the destruction caused by Cyclone Tracy in Moil. Shows debris amongst damaged houses.Unknown.Date:197

Close up of cyclone damage to house in the northern suburbs

Close up of cyclone damage to house in the northern suburbs. Rear view of damage to low set brick house, same house as in PH0026/0077.Unknown

Close up of cyclone damage to house in the northern suburbs

Close up of cyclone damage to house in the northern suburbs, shows damage to low set brick house.Unknown

Close up of cyclone damage to house in the northern suburbs

Close up of cyclone damage to house in the northern suburbs. Shows damage to low set brick house, possibly Nightcliff (ie water tower).Unknown

Close up of cyclone damage to house in the Northern Suburbs

Close up of cyclone damage to house in the Northern suburbs. Shows damage to low set brick house.Unknown

Close up of cyclone damage to house in the Northern Suburbs

Close up of cyclone damage to house in the Northern suburbs. Shows damage to low set brick house with push out windows.Unknown

Close up of cyclone damage to house in the Northern Suburbs

Close up of cyclone damage to house in the Northern suburbs. Shows damage to low set brick house with push-out windows.Unknown.Date:197