P.L. Chambers - Böcker

The first oral contraceptive became available in 1960 and since then these sub­ stances, which have been used by millions of women, have probably been the most widely studied group of drugs in medical history (Drill, 1966, 1977). Part of the evaluation oCoral contraceptives has involved their effect on the reproductive organs of women, with particular attention directed to evaluation of a possible carcinogenic effect of these steroids. To the extent that cancer of the reproductive organs is a common finding in women, the endogenous female sex hormones have been implicated in the occur­ rence of the cancer. The administration of estrogen has also been reported to in­ crease the incidence of cancer of the breast, cervix or endometrium in some strains or species of animals. Thus, because of the possible tumorigenic effect of estrogens there has been considerable interest in the relationship of oral contraceptives to cancer of the breast and genital tract.

Nervous system is in the most cases a likely target for the untoward effects of chemicals. The harmful consequences affect primarily the individual but may also considerably strain the whole society. The consumption of ethanol is a glaring example (National Institute on Alcohol Abuse and Alcoholism 1978). As ethanol, many organic liquids have similar immediate effects on the nervous system. The rapidity of the response suggests the involvement of the neuronal communication. The nervous system is also vulnerable to the depletion of oxygen, another common cause for the rapid deterioration of the brain function. It is quite impossible to list all the effects produced by the very large number of the individual chemicals. It would be more fruitful to try to understand the characteristics of the nervous system and the biochemical toxic mechanisms in the evaluation of the neurotoxicity of chemicals. Transfer of Xenobiotics in the Brain The adult central nervous system displays a functional barrier toward the blood-borne chemicals so that water-soluble compounds with an approximate molecular weight above 100 are largely prevented from directly entering the brain (Bradbury 1979). The functional barrier has morphological features typical to it and has a very close association of adjacent capillary cells separated by clefts of 12 A wide (Jacobs 1978). The nervous system capillaries are enveloped by glial cell tongues, and these pericytes contain contractile elements (Le Beux and Willemot 1978a, b) so that the capillaries can be constricted.

Many chemotherapeutic agents introduced for use in humans are carcinogenic in laboratory animals (Conklin et al. 1965; Shimkin et al. 1966; Griswold et al. 1968; Harris 1976). However, initially their beneficial effect in disseminated cancer was of such short duration that the inevitable death of the patient from his primary disease precluded any clinical manifestation of the carcinogenic potential. During the last decade, chemotherapy has radically changed the outlook for many patients with cancer. Combinations of drugs, administered as the primary treatment, have resulted in high rates of cure in patients with disseminated malignancies, such as stage IV Hodgkin's disease or childhood acute lymphocytic leukemia. In other disseminated forms of neoplasia, induction of a remission, a substantial palliation and a prolongation of survival have been achieved. In many instances of localised disease, where surgery with or without radiotherapy are the primary form of treatment, anticancer drugs have been used with success as adjuvant therapy for distant microscopic disease. With these spectacular achievements, secondary malignancies, in particular acute non-lymphocytic leukemia (ANLL), has become of major concern. Incidence Acute leukemia is the most frequent form of secondary neoplasia in patients treated for cancer (Penn 1981). In one large series, 5. 9% of all ANLL could be attributed to previous chemotherapy (Kapadia et al. 1980).