Ochratoxin A, a naturally occurring
mycotoxin, has recently been shown to cause renal and hepatic
carcinomas in mice. In the present studies, the effects of
ochratoxin A on immune mechanisms associated with
tumor resistance were examined in mice using dose levels similar to those that cause
neoplasia.
Ochratoxin A was shown to specifically inhibit natural killer (NK) cell activity and increase the growth of transplantable
tumor cells without altering T-cell- or macrophage-mediated antitumor activity. In contrast,
ochratoxin B, a much less toxic
ochratoxin, did not influence immune function. Polyinosinic:polycytidylic induced
interferon was markedly reduced in mice following exposure to
ochratoxin A although total
serum protein levels were slightly increased. Injection of polyinosinic:polycytidylic enhanced NK activity in the presence of
ochratoxin A, although the level of enhancement was slightly lower than that produced by the agent in the absence of
ochratoxin A. Thus,
ochratoxin appears to suppress NK cell activity by inhibiting production of basal
interferon. Additionally, these findings suggest a possible role for altered NK cell function in the development of
mycotoxin-induced
carcinogenesis.