Bracken fern poisoning

Extract

Poisoning of cattle by bracken fern (Pteridium aquilinum) has long been a serious problem on some of the poorer land where eradication of bracken is difficult or uneconomic. The problem occurs also on some better-class land since not infrequently cattle are used to crush out the bracken in the first stages of development of the land or to control regrowth of bracken after burning and sowing down pasture. Grazing horses have also been affected and both cattle and horses have at times heen poisoned whell stall fed on hay which contains bracken.     

Bracken poisoning and enzootic haematuria in cattle in China.

Acute bracken poisoning and enzootic haematuria are believed to have occurred in cattle in China for a long time. It is only in the past 10 years, however, that these diseases associated with the consumption of bracken ferns have been studied in detail and this paper reviews these recent studies. Based on a large scale survey, both conditions were found to be serious problems with a wide geographical distribution, especially in the mountainous regions of southwest China. Epidemiological and experimental work revealed that two species of bracken ferns, Pteridium aquilinum and Pteridium revolutum, were associated with these diseases, but the latter seems more important in China.     

Bracken toxicology: identification of some water soluble compounds from crozier and rhizome

The isolation and chemical characterisation of compounds not previously reported from bracken fern (Pteridium aquilinum L Kuhn) are described. They occurred in fractions derived from the plant which have been shown to be carcinogenic in mice. Known properties of structural analogues could have implications concerning initiation of tumour formation.     

rasH2 mouse: reproducibility and stability of carcinogenicity due to a standardized production and monitoring system

The rasH2 mouse was developed as a model for carcinogenicity studies in regulatory science. Its phenotype is stable during high-volume production and over successive generations. To produce rasH2 mice, three strains of mice (C57BL/6J-TgrasH2, C57BL/6J, and BALB/cByJ) were maintained individually. Since the homozygous c-HRAS genotype is lethal, hemizygous transgenic mice were maintained by crossing with inbred C57BL/6J mice. After breeding, male B6-transgenic mice were mated with female BALB/cByJ mice to obtain transgenic mice. Pups that were rasH2-Tg (tg/wt) or rasH2-Wt (wt/wt) were confirmed by genotyping. Frozen embryos were preserved by the Central Institute for Experimental Animals (CIEA) and sent to two facilities, CLEA Japan and Taconic Biosciences, where the mice were produced. Production colonies are created in both facilities and supplied to customers worldwide. To prevent genetic drift, the colonies were renewed for up to 10 generations, and renewals were carried out four times every five years from 2005 to 2021. To ensure the uniformity and maintenance of the phenotype of rasH2 mice, the carcinogen susceptibilities were monitored in every renewal of colonies by CIEA based on a standard protocol of the short-term carcinogenicity study using the positive control compound N-methyl-N-nitrosourea (MNU). Furthermore, simple carcinogenicity monitoring targeting the forestomach, the organ most sensitive to MNU, was performed approximately once a year. Based on the optimally designed production and monitoring systems, the quality of rasH2 mice with reproducibility and stability of carcinogenicity is maintained and supplied globally.     

Establishing a laboratory animal model from a transgenic animal: RasH2 mice as a model for carcinogenicity studies in regulatory science

Transgenic animal models have been used in small numbers in gene function studies in vivo for a period of time, but more recently, the use of a single transgenic animal model has been approved as a second species, 6-month alternative (to the routine 2-year, 2-animal model) used in short-term carcinogenicity studies for generating regulatory application data of new drugs. This article addresses many of the issues associated with the creation and use of one of these transgenic models, the rasH2 mouse, for regulatory science. The discussion includes strategies for mass producing mice with the same stable phenotype, including constructing the transgene, choosing a founder mouse, and controlling both the transgene and background genes; strategies for developing the model for regulatory science, including measurements of carcinogen susceptibility, stability of a large-scale production system, and monitoring for uniform carcinogenicity responses; and finally, efficient use of the transgenic animal model on study. Approximately 20% of mouse carcinogenicity studies for new drug applications in the United States currently use transgenic models, typically the rasH2 mouse. The rasH2 mouse could contribute to animal welfare by reducing the numbers of animals used as well as reducing the cost of carcinogenicity studies. A better understanding of the advantages and disadvantages of the transgenic rasH2 mouse will result in greater and more efficient use of this animal model in the future.