The replication of Nb 2 Node rat lymphoma cells in suspension culture is specifically stimulated by lactogenic hormones. Human (hPRL), ovine, bovine, and rat PRLs stimulated replication in a dose-dependent manner in the concentration range of 10 pg/ml to 1 ng/ml. Human, ovine, and bovine placental lactogens were similarly active. In addition, cell replication was stimulated by human GH (hGH), which is known to have lactogenic activity. Other hormones and growth factors examined were inactive. The growth stimulatory effects of hPRL and hGH were completely inhibited when excess anti-hPRL and anti-hGH, respectively, were added to the medium. A bioassay based on the response of the Nb 2 Node lymphoma cells to lactogenic hormones has been developed. Human serum stimulated cell replication. The effect was completely abolished if excess antibodies to both hPRL and hGH were present. The stimulation obtained with a number of human serum samples correlated very well with the sum of the hPRL and hGH concentrations in the sera, as determined by RIA (r = 0.95; P < 0.001). The concentrations of either hPRL or hGH in human serum could be individually determined by specifically blocking the growth stimulatory effect of the other hormone by adding excess anti-hGH or anti-hPRl. The sensitivity of this bioassay for PRL and hGH in serum exceeds that of RIAs.
In folklore medicine, extracts of the leaves of the subtropical plant Catharanthus roseus (L.) G. Don (sometimes known as Madagascar periwinkle) were reputed to be useful in the treatment of diabetes. This review describes how attempts to verify the antidiabetic properties of the extracts led instead to the discovery and isolation of two complex indole alkaloids, vinblastine and vincristine, which are used in the clinical treatment of a variety of cancers. The two alkaloids, although structurally almost identical, nevertheless differ markedly in the type of tumors that they affect and in their toxic properties. These and related alkaloids have been the subject of many pharmacological and biochemical investigations both in vivo and in vitro in the search for improved cancer treatments. A model system used in these studies, a transplantable lymphoma in Noble strain rats designated Nb2 node, has serendipitously led to the development of a highly sensitive and specific bioassay for lactogenic hormones.
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