Transplacental carcinogenesis

Abstract

This review shows that transplacental carcinogenesis has been quite extensively studied in several systems- ENU in the rat nervous system and mouse lung; DEN in the Syrian golden hamster trachea; DMBA in the mouse epidermis; and urethan in mouse ovary, liver and lung. With the exception of ENU, however, no compounds have been studied in detail for their metabolism or mode of interaction of their intermediates with macromolecules in the fetus. Many investigations have been carried out with MNU, DMN, BP and MC in relation to their metabolism, excretion and binding of intermediates to biological macromolecules in adult test systems, but very few studies of the transplacental carcinogenic potency of these compounds have been made. More coordinated experiments between laboratories are necessary to investigate transplacental carcinogenesis from the point of view of carcinogen metabolism, binding to fetal macromolecules, excretion and placental transfer. Little is known about the development stages of target organs for any given carcinogen in terms of proliferative activity of cells, activities of certain enzyme systems, degree of differentiation or phases of the cell cycle. It appears to be extremely important to define every aspect of the development stages of target organs - particularly if the results of animals experiments are to be related to the human situation. Comparative studies should be carried out on several species of laboratory animals including subhuman primates (Rice et al., 1979), which are considered suitable test systems. Transplacental carcinogenesis appears to be influenced by placental, maternal or immunological factors and to analyse these influences more precisely, it is necessary to investigate the direct response of target organs to carcinogens. Organ and cell culture provide unique opportunities to examine directly the effects of such exposure, particulary in human target organs, and it is of prime important that organ culture techniques for prenatal subjects are developed and improved.