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An act of design is a designer’s interaction within a group of designers. This group is characterized by instruments, competence and proficiency. Every act constitutes a round-trip between the designer group and a common base. Design is often conducted in a collective way. Points of view are often shared between contributors and decisions about different project aspects are submitted for common approbation.

It is now well established that neoplastic transformation results from progressive cell changes involving genes (Boyd and Barrett, 1990); it is then relevant to investigate the effects of particles on the cell structures carrying the genes. Several in vitro assays can be used allowing the detection of effects of potential carcinogens at the DNA and chromosome level. To use these assays as predictive or mechanistic models, one important point is to determine whether differences exist between cell responses to carcinogenic/non carcinogenic particles and why?

In a collaborative project which was supported by 96 transplant centers, DNA typing of HLA-DR antigens was carried out on over 7,000 transplant donors and recipients at 8 participating laboratories. Approximately 25% of the individuals were found to have been typed incorrectly by serological means. An analysis of over 2,500 first cadaver kidney transplants showed a significant correlation of matching for the HLA-DR antigens in transplants where the serological typing was confirmed by DNA typing. In transplants where the serological typing was found to be incorrect, the analysis of serological HLA-DR mismatches resulted in no correlation with graft outcome whereas a significant correlation was found when the corrected DNA typed HLA-DR antigens were analyzed. Transplants which had been reported to the Collaborative Transplant Study based on serological typing as matched for HLA-A, -B, -DR or HLA-B, -DR were found to have a superior graft survival rate only if HLA-DR compatibility was confirmed by DNA typing.

Inflammatory breast carcinoma (IBC) has long been accepted as a distinct subgroup of mammary cancer. Case reports appeared in the literature as early as 1814 [2] and the entity was formally described in 1924 [20]. It has been traditionally considered as an uncommon form that carries a particularly gloomy prognosis. There has, however, been considerable controversy with regard to the criteria that should be used for the diagnosis of this disease. In particular, conflicting information is to be found in the literature as to whether IBC is a clinical or pathologic diagnosis [11, 21]. In addition, recent reports have often included patients with IBC within a larger group of patients with locally advanced breast cancer. Despite these shortcomings, the treatment of IBC has evolved favorably over the last 15 years. The introduction of combination chemotherapy in the treatment strategy of IBC before local therapy has resulted in a substantial improvement in the outlook of this patient group.

Attapulgite and sepiolite are two clay minerals exhibiting fibrous shape and widely used over the world especially because of their remarkable sorptive and colloidal properties. Although these materials were considered as safe the biological effects observed with asbestos fibres have focused attention of scientists on the possible fibrogenic or carcinogenic potential of other fibrous minerals.

Exposure to Diesel exhaust can occur either in the general population or in occupationnal groups. Since a variety of mutagenic and carcinogenic substances have been identified from the gazeous and the particulate phases of Diesel exhaust, there is concern that such exposure might induce an excess of respiratory tract tumors. This concern has been substantiated by the recent finding of an increase in lung cancer risk in US (Garschik, 1987) or Canadian (Howe, 1983) railroad workers.Since pulmonary alveolar macrophage is endowed with an armamentarium with putative carcinogenic potencies, we have initiated a study assessing the effects of Diesel exhaust on alveolar macrophages. Cell reactivity was evaluated through assessment of release of arachidonic acid metabolites. In order to mimic physiological conditions, cells were cultured in gazeous phase. This enables the cells to be directly in contact with gazes. In addition, the respective role of the gazeous and the particulate phases of the Diesel exhaust were evaluated.

It has been reported recently that chrysotile fibres transform, in vitro, rat pleural mesothelial cells (RPMC) (Jaurand et al. 1984). This was demonstrated using an initiation-promotion model with benzo(a)pyrene (BP) as initiator and chrysotile fibres (Chr) as promoter. The data showed that BP and Chr were potent separately in inducing transformation of RPMC. In addition, there was no synergism between BP and Chr. In this study, the marker for transformation was altered morphology of colonies in liquid medium. As acquisition of anchorage-independent properties in vitro is a reliable marker for neoplastic conversion in some cell systems (Barrett et al. 1978; Shimada et al. 1983), the aim of the present work was to assess the ability of RPMC to growth in semi-solid medium (anchorage-independent conditions).

The cytotoxicity of mineral dusts, specially asbestos, has been studied in vitro with cell types from different origins and species. In our laboratory, we use rat pleural mesothelial cells (RPMC). From all data reported, there is a general agreement to conclude that treatment of cell cultures with chrysotile fibres induces an inhibition of cell growth (Wade et al. 1976, Neugut et al. 1978, Brown et al. 1978, Reiss et al. 1980, Jaurand et al. 1983, Mossman et al. 1983, Hesterberg et al. 1984, Hei et al. 1985, Lechner et al. 1985, Lu et al. 1988). This inhibition has been shown either from a reduction in cloning efficiency or from an increase in the mean population doubling time. With RPMC we have observed a dose dependent decrease in cell proliferation (Jaurand et al. 1983). This effect might be related to a cell killing and/or to an increase in the duration of the cell cycle. To test this second hypothesis we studied the cell cycle of normal RPMC and examined the effects of chrysotile on its regulation, either directly after treatment with chrysotile or indirectly after treatment with conditioned medium obtained from mesothelial cells transformed by chrysotile (Van der Meeren et al. 1988). In addition to the direct effects of asbestos fibres, treatment of cell cultures, including RPMC, with asbestos fibres results in a cell transformation and, in vivo, intrapleural inoculation or inhalation of chrysotile in rats results in occurrence of pleural mesothelioma (Wagner et la. 1969, Monchaux et al. 1981). It is known that transformed cells exhibit a different regulation of their proliferation when compared to their normal counterparts.

Cellular oncogenes (c-onc), homologous to retrovirus oncogenes, probably serving essential normal functions in development, differentiation or cell maintenance, can escape normal control under certain circumstances. Such genes when they become activated can initiate carcinogenesis (Astrin and Rothberg 1983).

Our industrial world is responsible for the emission of a great amount of respirable mineral dusts, either natural or artificially produced. This dust emission has become increasingly an important health problem, particularly in places of work where specific dusts were found to be responsible for severe lung diseases: silicosis, coal miner’s pneumoconiosis, berylliosis, hard metal lung fibrosis and asbestos-related diseases. Asbestos and other fibrous dusts are presently a major concern because of their carcinogenic potential [1,2].

Mesothelial cells are a useful model to study carcinogenesis related to mineral fibres (Lechner et al. 1985, Paterour et al. 1985a, Craighead et al. 1987, Mackay et al. 1987).

Historically, the series of workshops on “In Vitro Effects of Mineral Dusts” was initiated in 1979 by R.C. Brown, I.P. Gormley, M. Chamberlain and R. Davies at the MRC Pneumoconiosis Unit in Cardiff, Wales, U.K., with the main objective of exploring the possibilities of adapting to mineral dusts some in vitro short-term tests already currently in use in the field of chemical toxicology. At that time, the main preoccupation was to test asbestos fibres for their cytotoxicity. The cell systems used (red blood cells, peritoneal macrophages, various cell lines), were rather primitive. The second and third international workshops, held in the U.S.A. and F.R.G., respectively, clearly indicated that biologists were competing very successfully in order to find out the best cell systems specifically adapted to mineral dusts for studying not only cytotoxicity but also release of mediators by alveolar macrophages and their implication in fibrogenesis, and exploring genotoxicity and cell transformation. Two preoccupations were central to these research efforts: first, to understand mechanisms of pulmonary toxicology relating to inhaled mineral dusts; second, to obtain, if possible, ideal short-term tests for predicting the disease potentials of mineral dusts in animals and in humans. The fourth workshop has been entitled: “Effects of Mineral Dusts on Cells”, which indicates that, besides in vitro studies, we are involved with early and late in vivo responses, either in animals or in humans.

It is well known that carcinogens induce chromosomal changes after cell treatment in vitro. During a study on transforming potency of asbestos fibres and benzo-3-4-pyrene (BP) on rat pleural mesothelial cells, a chromosomal analysis has been carried out.

Mesothelial cells are target cells in asbestos-related carcinogenesis. Chrysotile fibers are known to induce mesothelioma in vivo (Wagner et al. 1969; Monchaux et al. 1981) and mesothelial cell transformation in vitro (Paterour et al. 1985).