ABSTRACT

Some years ago, we reported that low concentrations of superoxide or hydrogen peroxide were growth stimulatory when added to cultures of BHK-21 hamster fibroblasts (1). This now appears to be a wide-ranging phenomenon. A considerable variety of noninflammatory mammalian cells exhibit positive growth responses when exposed to low levels of exogenous superoxide or hydrogen peroxide (2). In our studies, while hydrogen peroxide stimulated the growth of both nontransformed and polyoma virus-transformed BHK cells, superoxide was notably stimulatory toward the tumor virus-transformed cells. Differences in growth stimulatory responses elicited by exogenously added superoxide and hydrogen peroxide have been observed by others (3). In the case of superoxide, certain of its effects, such as increasing intracellular pH and calcium, are extremely rapid and can be inhibited by anion-channel blockers. Hydrogen peroxide, which can permeate cell membranes, does not elicit these early growth-related changes but, in common with superoxide, can upregulate the expression of "early growth response genes."