In vitro studies on the anemia of tumor-bearing hamsters.

T HE POSSIBILITY that the anemia in some cancer patients was due to the hemolytic effect of toxins produced by the tumor was first analyzed by Weil2#{176} in 1908. He demonstrated that extracts of normal human and animal organs had a lytic effect in vitro on red blood cells although there was considerable variability in the hemolytic potency of these extracts. Moreover, he reported that both necrotic and non-necrotic tumors had some hemolytic effect, with more hemolysis produced by the necrotic tumors. Weil concluded from these studies that the anemias associated with malignant tumors were probably due in part to the direct hemolytic action of products of necrosis in the tumor. Gross7#{176} reported that heniolysis of the donor’s red blood cells could be produced in vitro by a saline-extracted, filtrable, thermolabile substance derived tinder aseptic conditions from mouse and human neoplasms. He extracted his lytic material from tumors which were primarily composed of viable-appearing tumor tissue. There was no separation of the extracts obtamed from necrotic and from healthy tumor tissue. Other investigators’5’10’12’14’#{176} have reported hemolysins to be present in extracts derived from tumor tissue. Ponder and Nesmith14 and Br#{252}chmann and Westheimer5 suggested that these hemolysins were derived from the necrotic foci within growing tumors. In studies reported by Sherman18 concerning the development of anemia in nontumor-bearing hamsters it was found that repeated injections of an extract of necrotic tumor tissue could produce an anemia in hamsters comparable to that found in tumor-bearing animals.17 It was also shown that repeated injections of an extract of apparently viable tumor tissue did not produce this effect. It was felt that the anemia was probably relateti to an immunologic response to the altered or “foreign” proteins found in the necrotic homologous tumor tissue. However, the possibility of direct destruction of red blood cells by lytic agents found in the necrotic portions of growing tumors could not be ruled out. It was, therefore, decided to investigate the hemolytic effect in vitro of extracts of whole tumor and also of extracts of both the necrotic and the viable portions of these same tumors when they were separately extracted. The hemolytic effect in vitro of extracts of normal organs from nontumor bearing hamsters was also studied.