Toxic exposures proliferation

Persistent activation of PPARa can induce the development of hepatocellular carcinoma in susceptible rodent species by a nongenotoxic mechanism, i.e., one that does not involve direct DNA damage by peroxisome proliferator chemicals or their metabolites. This hepatocarcinogenic response is abolished in mice deficient in PPARa, underscoring the central role of PPARa, as opposed to that of two other mammalian PPAR forms (PPARy and PPAR5), in peroxisome proliferator chemical-induced hepatocarcinogenesis. Other toxic responses, such as kidney and testicular toxicities caused by exposure to certain phthalate... 

Several studies have suggested that some critical adverse effects like peroxisome proliferation, hepatotoxicity, immunotoxicity, and developmental toxicity may be associated with chemical exposure to PFCs, particularly to PFOS (perfluorooctane sulfonate) and PFOA (perfluorooctanoic acid), two ubiquitous persistent organic pollutants with possible environmental and human health risks. 

Controversial results were reported by Warheit et al. in two studies [57, 65] in which rats were exposed to raw SWNTs. Cell proliferation and cytotoxicity indices indicated that exposure to SWNTs produced only transient inflammation. Histological examination of exposed animals, however, identified the development of granulomas, which were non-dose dependent, nonuniform in distribution and not progressive after 1 month. The presence of granulomas was considered inconsistent with the lack of severe lung inflammation. These two reports highlighted the need for more research on the potential pulmonary toxicity of CNTs, shifting the scientific focus towards this aim. 

The immunotoxicology of metals in fishes has been reviewed elsewhere [74-76, 45], Overall, the immune systems of fishes are highly sensitive to metals, although the effects are not always suppression of immune functions. Burnett [76] demonstrated that low levels of metals increased intracellular calcium, increased protein phosphorylation, and stimulated lymphocyte proliferation in fish. Since most metals are toxic to both the nervous system and the immune system, a neuroendocrine-immune link to immuno-toxicity from metal exposure is likely. 

Larson et al. (1996) investigated the ability of intermediate exposure to chloroform vapors to produce toxicity and regenerative cell proliferation in the nasal passage of male and female B6C3Fi mice. Groups of 8 animals of each sex were exposed to 0, 0.3, 2, 10, 30, or 90 ppm chloroform via inhalation for 6 hours a day, 7 days a week for 3, 6, or 13 weeks additional groups of 8 animals of each sex were exposed for... 

Larson and coworkers (1996) investigated the ability of intermediate-duration chloroform vapor exposure to produce toxicity and regenerative cell proliferation in the liver of male and female B6C3F, mice. 

In an earlier study, Larson et al. (1994c) examined the ability of chloroform vapors to produce toxicity and regenerative cell proliferation in the liver and kidneys of female B6C3F, mice and male Fischer 344 rats, respectively. Groups of 5 animals were exposed to 0, 1, 3, 10, 30, 100, or 300 ppm chloroform via inhalation for 6 hours a day for 7 consecutive days. Actual exposure concentrations measured for mice were 0, 1.2, 3, 10, 29.5, 101, and 288 ppm and for rats were 0, 1.5, 3.1, 10.4, 29.3, 100, and 271 ppm. Necropsies were performed on day 8. The kidneys of mice were affected only at the 300 ppm exposure, with approximately half of the proximal tubules lined by regenerating epithelium and an increased LI of tubule cells of 8-fold over controls. In the kidneys of male rats exposed to 300 ppm, about 25-50% of the proximal tubules were lined by regenerating epithelium. The LI for tubule cells in the cortex was increased at 30 ppm and above. 

The sequel to acute injury depends on the potency and concentration of the toxic agent and the duration of exposure. Potent gases produce a severe vascular reaction and alveolar flooding. The fluid prevents gaseous exchange, and death of the human or animal ensues. After acute mild nonlethal damage, excess fluid is removed and the resistant Type II cells proliferate and reline the alveoli. The cells subsequently differentiate into Type I cells. 

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