Search PubMed⌕ Search

Biomedical subjects

J M Rice

Publications and source records attributed to J M Rice.

220 records · Page 13Linked to original sources
PubMedDate not supplied

Tumors of the nervous system in carcinogenic hazard identification.

In the absence of adequate data on humans, it is biologically plausible and prudent to regard agents and mixtures for which there is sufficient evidence of carcinogenicity in experimental animals, usually rats and mice, as if they presented a carcinogenic risk to humans. Prediction of cancer sites in humans from bioassay data in rodents is much less certain, however, regardless of organ or tissue. For tumors of the nervous system, there is practically no basis for judging the validity of such predictions, as only ionizing radiation is known to cause tumors of the central nervous system (CNS) in humans. Brain tumors are relatively uncommon findings in bioassays and are rare in untreated rodents, even in rats, which appear to be the most susceptible species. However, CNS tumors have been readily induced in rodents by systemic exposures to some chemicals, notably N-nitrosoalkylureas and other alkylating agents and certain alkyl hydrazine derivatives. CNS tumors in rodents have played a significant role in carcinogenic hazard evaluations of several other chemicals, including acrylonitrile, ethylene oxide, and acrylamide, and have been implicated as part of the tumor spectrum induced by vinyl chloride and certain inorganic lead compounds. In some of these evaluations, it is not certain that all tumors diagnosed as primary brain tumors were correctly identified. Diagnostic difficulties have been presented by undifferentiated small-cell tumors that may invade the brain, including carcinomas of the nasal cavity and undifferentiated schwannomas arising in cranial nerve ganglia, and by the difficulty of reliably distinguishing between focal reactive gliosis and early glial neoplasms. The most striking experimental finding regarding the induction by chemicals of tumors of the nervous system is the dramatically greater susceptibility of the fetal and neonatal nervous system to some carcinogens, as compared with the susceptibility of the nervous system in adults of the same species.

Animals↗
PubMedDate not supplied

Dissimilar frequency of hepatoblastomas and hepatic cystadenomas and adenocarcinomas arising in hepatocellular neoplasms of D2B6F1 mice initiated with N-nitrosodiethylamine and subsequently given Aroclor-1254, dichlorodiphenyltrichloroethane, or phenobarbital.

Aroclor-1254 (Ar-1254) and dichlorodiphenyltrichloroethane (DDT) were compared to phenobarbital (PB) for their ability to promote hepatocellular proliferative lesions to hepatocellular adenomas and carcinomas and to hepatoblastomas in D2B6F1 male mice initiated with N-nitrosodiethylamine (NDEA). Hepatocellular neoplasms developed in all mice given NDEA and were more numerous in mice fed promoters. Multiplicities decreased in the order Ar-1254 > PB > DDT, indicating that Ar-1254 was more potent than either PB or DDT at the dosage levels used. PB was the most effective of the 3 agents in stimulating the evolution of hepatocellular neoplasms to hepatoblastoma. The incidence of hepatoblastomas in the NDEA.PB group was 72% but was only 27% in NDEA-initiated, DDT-promoted mice and 33% in low-dose and only 9% in high-dose Ar-1254-promoted mice. In contrast, lesions resembling benign and malignant cholangiocellular neoplasms were frequently found within hepatocellular tumors in Ar-1254-promoted mice but not in mice fed PB or DDT, either alone or after NDEA. Some cystic glandular structures in Ar-1254-promoted mice contained mucous cells, argentaffin cells, and Paneth cells and thus constituted intestinal metaplasia. Hepatoblastoma and intestinal metaplasia/cholangiocellular tumor morphology appear to constitute different patterns of genetic programming induced by certain promoters in expanding clones of initiated hepatocytes, on favorable genetic backgrounds such as that of D2B6F1 male mice.

Adenocarcinoma↗
PubMedDate not supplied

Liver tumorigenesis by Helicobacter hepaticus: considerations of mechanism.

A new animal model for the causation of liver tumors via a bacterial infection presented itself fortuitously in the form of a new species, Helicobacter hepaticus. This species of Helicobacter colonizes the hepatic bile canaliculi in susceptible strains of mice, resulting in hepatitis and hepatocellular and hepatocholangiolar adenomas and carcinomas. The mechanism by which this infection leads to cancer is unknown. Tests with Helicobacter hepaticus have revealed thus far that the bacteria do not secrete a mutagen which is capable of detection by the Ames Assay. Measurement of oxidatively damaged bases in the liver DNA of hepaticus infected mice have shown accumulation of 8-oxodeoxyguanosine with disease progression. Other promutagenic DNA lesions, 7-methylguanine and O6-methylguanine, indicative of nitrosation of endogenous amines by nitric oxide, were not detected. Analysis of carcinomas and adenomas taken from H. hepaticus infected A/JCr mice revealed no mutations in ras oncogenes or in exons 5-8 of the p53 gene. These preliminary results indicate that a non-genotoxic tumor promotion mechanism, possibly implemented by reactive oxygen species from the immune response, is more likely than a genotoxic mechanism.

Alkylation↗