Most impoant dose-limiting toxicity of cancer chemotherapy is:

G E N ERAL TOXICITY OF CYTOTOXIC DRUGS Majority of the cytotoxic drugs have more profound effect on rapidly multiplying cells, because the most impoant target of action are the nucleic acids and their precursors; rapid nucleic acid synthesis occurs during cell division. Many cancers (especially large solid tumours) have a lower growth fraction (lower percentage of cells are in division) than normal bone marrow, epithelial linings, reticuloendothelial (RE) system and gonads. These tissues are paicularly affected in a dose-dependent manner by majority of drugs; though, there are differences in susceptibility to individual members. 1 . Bone marrow Depression of bone marrow results in granulocytopenia, agranulocytosis, thrombocytopenia, aplastic anaemia. This is the most serious toxicity; often limits the dose that can be employed. Infections and bleeding are the usual complications. 2. Lymphoreticular tissue Lymphocytopenia and inhibition of lymphocyte function results in suppression of cell mediated as well as humoral immunity. Because of action (1) and (2) + damage to epithelial surfaces, the host defence mechanisms (specific as well as nonspecific) are broken down