Hyperplastic toxicity

The term "hyperplastic toxicity" is used in this presentation to describe toxicity-induced cell proliferation associated with increased mitotic activity, increased DNA (as judged by increased density of nuclear chromatin staining or indicia of increased DNA synthesis) and other changes associated with enzyme and membrane functions which are not of a malignant nature per se. 

Not all compounds which induce hyperplasia can act as tumor promoters, thus while the phenomena associated with tumor promotion include hyperplastic changes, hyperplasia per se is not precisely the same phenomenon as promotion. However, certain patterns of hyperplastic toxicity appear to be identical and coincidental with certain biological phenomena observed to occur when the classical tumor promoters are administered to... 

In rats ammonium perfluorooctanoate induced hepatomegaly that was more pronounced in the male than in the female. Male rats are thought to be more sensitive to the toxic effects of ammonium perfluorooctanoate because of their slower excretion rate. The rapid excretion by female rats is due to active renal tubular secretion, which is considered to be hormonally controlled by estradiol and testosterone levels. The hepatomegaly was hypertrophic rather than hyperplastic and involved proliferation of peroxisomes. 

Similarly, no respiratory effects were found in rats and mice chronically exposed by diet to 5/ 10" and 1.3 10s g/kg/day of 2,7-DCDD, respectively (NCI/NTP 1979a). In contrast, rats exposed chronically by gavage to a mixture of 1,2,3,6,7,8-HxCDD and 1,2,3,7,8,9-HxCDD at 0.18, 0.34, and 0.7 g/kg/day had a dose-related increased incidence of adenomatous hyperplastic lesions in terminal bronchioles and adjacent alveoli of both males and females no such effects were found in mice exposed chronically to 0.7 g/kg/day of that same mixture (NCI/NTP 1980). The existing information suggests that in animals, the respiratory system is not a sensitive target for CDDs toxicity via oral exposure. 

Hematological Effects. Both human and animal studies have shown that benzene exerts toxic effects on various parts of the hematological system. All the major types of blood cells are susceptible (erythrocytes, leukocytes, and platelets). In the less severe cases of toxicity, specific deficiencies occur in individual types of blood elements. A more severe effect occurs when there is hypoplasia of the bone marrow, or hypercellular marrow exhibiting ineffective hematopoiesis so that all types of blood cells are found in reduced numbers. This is known as pancytopenia. A biphasic response (i.e., a hyperplastic effect in addition to destruction of the bone marrow cells) has been observed (Aksoy et al. 1972, 1974 Doskin... 

The antipsychotic agents are known to precipitate proteins and may coprecipitate polynucleotides so they can no longer participate in nucleic acid synthesis. Chlorpromazme also increases the loss of macromolecules from the intracellular pools that are essential for cellular replication. When the hone marrow from a patient with phenothiazine-induced agranulocytosis is examined, it initially appears to have no cellularity (aplastic), hut over time it becomes hyperplastic. It is believed that toxic effects of the phenothiazines are not seen in all patients taking the medications because the majority of patients have enough bone marrow reserve to overcome the toxic effects. ... 

Rhesus monkeys were exposed to PCB 52 or PCB 77 in estimated dietary doses of 0 or 60 pg/kg/day for 133 days (McNulty et al. 1980). Pathologic changes, including dilation of the extrahepatic biliary tree and hyperplastic intrahepatic biliary vessels, were induced by PCB 77 but not PCB 52. Additional liver data were not obtained for PCB 77 due to high systemic toxicity manifested as clinical signs, general emaciation, and marked effects in nonhepatic tissues. 

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