Streptozotocin is not toxic to the human fetal B cell

Abstract

It has been generally assumed that because streptozotocin is toxic to the adult B cell of most species, it should also damage B cells obtained at earlier stages of development. This paper examines whether this is true for human fetal pancreata obtained from the therapeutic termination of pregnancies during the first half of the second trimester. Experiments were carried out both in vivo and in vitro. For the former experiments diced expiants of the human fetal pancreas were grafted beneath the renal capsule of nude mice 3 weeks before Streptozotocin was administered to make the animals diabetic. The grafts were removed 1 week, 2-4 weeks or 3 months later, and were found to be of similar weight and insulin content to the control grafts. In 2 of the animals with grafts remaining for 3 months the diabetes had even been reversed by the implant, hyperglycaemia recurring when the graft was removed. In contrast, rat fetal pancreata grafted beneath the renal capsule of nude mice, subsequently rendered diabetic, were adversely affected by Streptozotocin, the insulin content of the implants being 12% of levels in control grafts. Adequate uptake of Streptozotocin by the implanted human fetal pancreas was established by measuring tissue levels of the drug 30 min after its injection. Histological examination of the grafted human fetal pancreas showed no deleterious effect of Streptozotocin on the number of granulated B cells one day after injection, although by this time the host was diabetic. In vitro, Streptozotocin had no effect on insulin release from the cultured human fetal pancreas, whereas a toxic effect on adult mouse islets was observed. In summary, these data show that Streptozotocin has no demonstrable diabetogenic effect on the human fetal B cell, a situation comparable to the lack of chemotherapeutic effect of this drug in many patients with malignant insulinomas, which morphologically and functionally have some similarities with the human fetal pancreas. © 1989 Springer-Verlag.