Environmental risk factors for osteoporosis.

The experiments aimed at evaluating the optimal parameters in the chemo-immunotherapeutic treatment of the L1210 lymphoid leukaemia grafted to [female BALB/c (H2d) x male DBA/2 (H2d)]Fl hybrid mice, hereafter referred to as CDF1 mice. In vitro irradiation of leukaemic ascites cells by X-or y-rays and subsequent inoculation in mice showed that optimum immunogenicity is radiation dose-dependent. Grafting mice with l07 leukaemic ascites cells irradiated at optimum dose (80 GyX-or y-rays) delays mortality of the animals when challenged later with untreated L1210 cells, but is unable to cure mice. By contrast, specific immunoprophylaxis induced by Micrococcus, complement-triggering polysaccharides or BCG and irradiated leu-kaemic cells was able to protect mice against grafts of 104 L1210 cells. The i.p. route was notably superior to the i.v. route. When mice bearing advanced L1210 tumour were treated by chemotherapy (12 mg/ kg of BCNU) on Day 6 5 after grafting 104 L1210 cells and subsequently treated by immunotherapy, a very high percentage (up to 90o%) of mice with 108 leukaemic cells could be cured by repeated 1 mg injections of bacterium or polysaccharide, and challenge with irradiated leukaemic cells was unnecessary. Because of the high cure rate obtained, the very regular response pattern and the non-pathogenicity, the bacterium Micrococcus Iysodeikticus would seem a promising new candidate for chemo-immunotherapeutic antitumour strategies. THE BCG STRAIN of Mycobacterium bovis has become a popular agent for immunotherapy of cancer. However, the general use of BCG is made difficult because of many disadvantages: BCG can cause ulceration, pyrexia, abnormal liver function, tuberculosis and, in a few reported cases, death or even enhancement of Micrococcus lysodeikticus is a non-pathogenic and easy-to-eliminate (sub-strate of lysozyme) Gram-positive bacterium , that elicits the production of large amounts of antibodies of restricted hetero-geneity and clonal dominance in rabbits (Van Hoegaerden et al., 1975) and mice (Verloes et al., 1977a; b). Since antimicro-coccus antibodies are directed against carbohydrates (Wikler, 1975) and bind to certain lymphocytes (Verloes & Kanarek, 1976; De Baetselier et al., 1977) and to several tumour-cell types (L1210 lymphoid cells, Ehrlich carcinoma cells) (Verloes et al., 1976) but not to erythrocytes (Verloes et al., 1979a), they are believed to act on cells in a similar way to the lectins but with greater discrimination and less t To wloom requests for reprints and correspondence sbould be addressed.