What are the effects of hydrogen peroxide on slow- and fast-growing NIH/3T3-derived cultures in relation to cellular senescence and transformation?

Hydrogen peroxide (H₂O₂) is a reactive oxygen species (ROS) that can induce oxidative stress in cells. Oxidative stress has been implicated in cellular senescence, which is a state of irreversible cell cycle arrest, and in cellular transformation, which can lead to tumorigenesis. The study investigates the effects of hydrogen peroxide on two types of NIH/3T3-derived cultures: NIHs (fast-growing, transformed phenotype) and NIHv (slow-growing, senescent phenotype), compared to the reference NIHb culture (normal proliferative state). The aim is to understand how hydrogen peroxide modulates cellular senescence and transformation by comparing these different proliferative states.

Hydrogen peroxide induces different responses in NIHs and NIHv cells, which are related to their basal proliferative activities and redox states. In NIHs cells, hydrogen peroxide treatment leads to a significant decrease in proliferative activity, increased expression of senescence-associated markers (e.g., SA-β-galactosidase positivity), and changes in mitochondrial and lysosomal content/activity. These changes are indicative of the acquisition of a senescent phenotype. In NIHv cells, which are already in a senescent state, hydrogen peroxide treatment further reduces proliferative activity and increases the accumulation of lipofuscin, a marker of cellular aging. The treatment also affects the mitochondrial and lysosomal compartments, suggesting that hydrogen peroxide can modulate senescence and transformation through redox-dependent mechanisms. The study concludes that hydrogen peroxide can induce senescence in transformed cells and modulate the senescence state in already senescent cells, highlighting the complex interplay between oxidative stress, cellular senescence, and transformation.