Skin tumorigenic potential of aflatoxin B1 in mice.

Aflatoxin B1 (AFB1) has been classified as a category I human carcinogen, which is responsible for a high incidence of hepatocellular carcinoma. Since exposure to AFB1 can occur through skin contact in addition to ingestion and inhalation, the carcinogenic potential of topically applied AFB1 on mouse skin was investigated. Our results show that single topical application of AFB1 (80 nmol) as a tumor initiator, followed by twice weekly application of 12-tetradecanoyl phorbol myristate acetate (TPA, 4 nmol), resulted in tumor formation after 13 weeks. However, no tumorigenic potential was observed when AFB1 (16 nmol) was used either as a complete carcinogen or as a tumor promoter (4 nmol). Histological analysis of skin showed squamous cell carcinoma in the AFB1/TPA treated group. The application of AFB1 as a complete carcinogen, an initiator or a promoter after 24 weeks demonstrated widespread degenerative and necrotic changes in hepatic tissue as well, suggesting liver to be the target organ following percutaneous absorption. Additionally, twice weekly topical application of AFB1 caused significant induction of cutaneous CYP IA monoxygenases without any effect on hepatic levels while glutathione-S-transferase activity was induced more in the liver than skin. The topical application of AFB1 also resulted in increased hepatic and cutaneous lipid peroxidation with concomitant depletion of glutathione content. It is likely that due to higher induction of hepatic GST activity, products of lipid peroxidation may be detoxified and therefore unable to cause DNA damage making mice resistant to hepatic tumor formation. The overall results indicate a tumor initiating potential of AFB1 in mice and suggest that continued dermal exposure of AFB1, even at low doses, might lead to degenerative changes in hepatocytes.

Prevention of acute cadmium toxicity by Picroliv.

The potential of Picroliv, a herbal extract against acute cadmium (Cd) intoxication, was evaluated in male rats. Biochemical and histopathological profile in rats pretreated with Picroliv (12 mg/kg, oral) followed by a single dose of Cd as cadmium chloride (CdCl2) (3 mg/kg, ip) revealed marked suppression of oxidative stress in liver and testes. The Cd-induced enhanced levels of lipid peroxidation, membrane fluidity and reduced levels of nonprotein sulphydryls and Na(+)K(+)ATPase were significantly restored to near normal by Picroliv pretreatment. In addition, the Cd-induced serum levels of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, gamma glutamyl transpeptidase and lactate dehydrogenase were restored to near basal levels. Hepatic and testicular histopathological damage was also minimized. The results strongly suggest definite hepato- and testicular protection by Picroliv. The antioxidant potential of the herbal extract in the major part, and not its chelating property, seems to be responsible for its ameliorative action.

Effect of talc injected intravenously in guinea pigs.

The pulmonary angiothrombotic lesions in narcotic addicts attributed to the talc present in drug tablets were studied experimentally in guinea pigs following repeated intravenous administration of a suspension of talc dust (75 mg per animal). In early periods there was a moderate localization of talc particles in the alveolar capillaries of lung, liver and abdominal lymph nodes. The vascular injury in the pulmonary tissue was in the form of mild proliferation of the endothelial cells. In addition, many nodular collections comprising macrophages and lymphocytes developed around such vascular structures. At later periods (150 days) the only significant reaction obtained was moderate thickening of interalveolar septa and the lesions were in no way comparable to the human reports. The significance of these findings has been discussed.

Effect of intratracheal injection of mica dust on the lymph nodes of guinea pigs.

Histopathological changes in the tracheo-bronchial lymph nodes were studied up to 365 days in guinea pigs following intratracheal injection of a suspension of mica dust. In general, the cytotoxic effect provoked by dust was not pronounced as the majority of the swollen dust-laden macrophages retained their normal structure at the termination of the experiment and fibrotic lesions were limited to the formation of thick reticulin fibers. The poor fibrogenic response of mica dust has been attributed to its low cytotoxicity.

Coir fibre toxicity: in vivo and in vitro studies.

The biological activity of coir fibre, coir ash and their components were investigated in vitro by measuring the haemolytic activity and macrophage cytotoxicity. In vivo studies carried out by injecting guinea pigs intratracheally with coir fibres resulted in resolving granulomas. The observed haemolytic activity and macrophage cytotoxicity was more marked with coir ash compared with coir fibres. Chemical analysis of coir ash revealed the presence of toxic chemical constituents in appreciable amounts.

Pleural plaques in asbestosis: effect of Candida albicans.

Effect of chrysotile dust alone or together with Candida albicans administered intratracheally in guinea pigs was studied in the genesis of pleural plaques over a period of 12 months. A significant increase of mucopolysaccharides, phosphorus, calcium and -SH content was detected in pleural fluid of animals treated with chrysotile and Candida albicans together than in those treated with chrysotile or Candida albicans alone. The results suggest that an infection of Candida albicans accentuates the effect of chrysotile by altering the biochemical parameters preceding to the formation of pleural plaques.

Neutron activation analysis of respirable mica samples and their pathological effects in lungs of rats.

Instrumental and radiochemical neutron activation analyses (INAA, RNAA) have been used to quantify the different elements present in mica samples derived from Indian mines and a factory, together with USGS standards using high-resolution gamma-ray spectrometry. Both samples revealed the presence of several toxic elements in appreciable quantities. When tested in a rat model system over a period of 360 days after intratracheal injection of mica samples of respirable size (50 mg/animal), the animals which received the factory sample containing shellac exhibited enhanced dust-induced pulmonary reaction together with characteristic abscess formation at later periods. The significance of these findings is discussed.

Exacerbation of soft tissue lesions in lead exposed virus infected mice.

OBJECTIVE: To investigate the effect of Lead (Pb) acetate exposure on Semliki forest virus (SFV) pathogenesis in mice. METHODS: Different doses (62.5, 125, 250 and 500 mg/Kg body weight) of Pb dissolved in normal saline were given to mice by oral intubation in a sub-acute (28 days) and sub-chronic (90 days) regimen followed by SFV infection. Morbidity, mortality, clinical symptoms, mean survival time (MST), changes in body and organ weight, accumulation of lead in soft tissues, virus titre in brain and histopathological alterations were compared between lead exposed and infected groups. RESULTS: Early appearance of virus symptoms, increased mortality, decreased MST, enhanced SFV titre and greater tissue damage were observed in lead exposed-SFV-infected mice. CONCLUSION: Pre-exposure to lead increases the susceptibility of mice towards SFV infection. Further studies are suggested in view of the persistence of lead in the environment and the possibility of infection by microbial pathogens.

An evaluation of the environmental implications of petroleum refinery emissions by multielemental neutron activation analysis of rumen fluid ash of buffaloes.

In order to study environmental pollution in and around a petroleum refinery complex, a multielemental instrumental neutron activation analysis (INAA) method was used to assay concentrations of As, Ba, Br, Cl, Co, Cr, Cs, Cu, Fe, Hg, La, Mn, Mo, K, Na, P, Sc, Rb, Se, Sr, W and Zn in the rumen fluid ash samples of buffaloes from the vicinity of the refinery. Corresponding samples from a control area 300 km away from the refinery were analysed. Standard Reference Materials, Bovine liver (SRM 1577a), Oyster tissue (SRM 1566a) and Animal bone (CRM H-5) were also analysed for quality control. Samples were irradiated with thermal neutrons at 10(12)-10(13) n cm-2 s-1 and counted by high-resolution gamma spectrometry. Mean elemental concentrations of As, Ba, Br, Cr, Hg and Fe were found to be enhanced, whereas those of Na, K, Cl, Cu, Mn and P were depleted in samples from the vicinity of the refinery complex compared to controls. The environmental implications of anomalous elemental concentrations are discussed.

Modulatory effects of metanil yellow on immunity in rodents.

Pathomorphological and immunological studies were carried out on rodents following oral administration of 0, 0.1, 0.25 and 0.5% (w/w) metanil yellow, mixed in diet, for 30 days. No significant change in hematologic parameters and histologic architecture of liver, kidney, mesenteric lymph node, thymus and urinary bladder was observed except for mild desquamation of intestinal villi and moderate changes in Peyer's patches of small intestine with higher doses. Among immunological parameters, significant enhancement in the primary humoral immune response (anti-SRBC IgM plaque forming cells of spleen) was observed with the lowest dose of metanil yellow while higher doses produced opposing effects. An elevated cutaneous delayed type hypersensitivity (DTH) reaction to SRBC was seen in 0.1% metanil yellow treated animals but higher doses did not influence the reaction. The treatment also caused changes in functional capabilities of macrophages. Although these immune alterations could hardly influence the local immunity of gut, as measured by the capacity of animals to cause rejection of Nippostrongylus brasiliensis parasite, the potential to modulate the immunity in general by metanil yellow however assumes considerable biological significance.

Styrene induced pancreatic changes in rodents.

Subchronic oral exposure to styrene in rodents (25 or 50 mg/kg/day in mice; 160 or 320 mg/kg/day in rats and guinea pigs, 5 days/week) for 4 weeks resulted in moderate congestion of pancreatic lobules, focal inflammatory reactions around islets (in mice) and altered serum insulin level while blood glucose levels remained unaffected. Increased beta cell degranulation together with characteristic neoformation of islets were predominantly seen in pancreas of guinea pigs.