An alternative animal model for perinatal carcinogenesis.

The differences in developmental biology between marsupials and eutherian animals provide alternative approaches to major problems in perinatal carcinogenesis. The high susceptibility of the neonatal American marsupial, the opossum (Didelphis virginiana), during early postnatal development to oral, chemical induction of dysontogenetic tumors with a close morphologic and biologic resemblance to those in the human suggests that the neonatal marsupial may offer unique opportunities for the study of carcinogenesis during ontogenesis without placental interference and under a maternal influence limited to the constituents of milk and contact with skin secretions. Although there is as yet no experimental data on transplacental tumor induction in the marsupial, several aspects of marsupial gestation, including a primitive yolk sac placenta devoid of implantation and an apparent, partial nutritional autonomy of the developing fetus, imply that the marsupial in utero may, like the marsupial neonate, be more accessible to tumor induction than its eutherian counterpart. The results of preliminary attempts to develop pre- and postnatal life support systems (embryo culture and an artificial marsupium) suggest the feasibility of further reducing maternal influence on the developing marsupial in order to enhance the utility of the model. Currently, the opossum and the marsupial mouse (Sminthopsis macroura) appear to be the marsupials of choice for perinatal carcinogenesis experiments.

Toxicity of polybrominated biphenyls (PBBs) in Domestic and laboratory animals.

The composition, environmental fate, and effects of the polybrominated biphenyls (Firemaster BP-6 or FF-1) involved in the accidental contamination of cattle feed in Michigan in 1973 are reviewed. Toxic effects referred to in this report are limited to those occurring in domestic and laboratory animals and include general toxicity, neurobehavioral toxicity, immunotoxicity, reproductive toxicity, mutagenicity and carcinogenicity. The absorption, distribution, biotransformation and elimination of these polybrominated biphenyls are discussed along with the interactions with other chemicals and drugs.

Health effects of coal mining and combustion: carcinogens and cofactors.

Some polynuclear aromatics (PNA) have been found to be potent carcinogens for all tissues and organs of experimental animals that have been exposed to them, but different dose levels are needed for these effects. They have been known for decades to cause cancer at the site of application but also at certain sites distant from the area of contact. Although some hydrocarbons are potent and complete carcinogens, the majority of related hydrocarbons was originally found to be inactive. Since they generally appear together, it was important to know more about their interaction, particularly whether they would synergize, or antagonize. The polycyclic hydrocarbons have been studied by subcutaneous injection, where they prove very potent carcinogens. They are also very active on the skin of mice where they produce cancer on prolonged application. Inhalation studies, require larger doses yielded negative results until particulate matter was introduced which facilitated the development of lung tumors. Although iron oxide dust was used initially, other dusts were also capable of enhancing the response of the tissue to benzo(a)pyrene carcinogenesis. This point is of importance, particularly since the inhalation of PNA in situations of air pollution or coal mining involves particulates, although of a different type. Soot is not a homogenous substance and several factors determine its properties. Soots will lose some of the absorbed chemicals during their residence in air, but they retain their PNAs for long periods of time when they reach the soil. The carcinogenicity of PNAs in the adsorbed state may be completely absent, depending on particle size of the soot and availability of eluting capability of the tissues or cells in contact with the soot. Whenever the carcinogenic polynuclear aromatics can be eluted they will be active in producing cancer if their residence is adequate. There seems to be no reason to assume that a large increase in coal combustion in the future will by necessity lead to greater risks of cancer to the coal miners or the general urban dweller, because activities to be started now can take into consideration the requirements necessary for control of air pollution in mines as well as in cities. If new uses of coal will be developed, it will be a completely different situation, and statements about the carcinogenic risk from coal utilization do not apply there. Although some of the same carcinogenic PNAs are involved in the health hazards from those processes, other carcinogens and also cocarcinogens will be present, and the exposed workers will not have the apparent benefits of adsorption of PNAs on soot.

Tissue differentiation and susceptibility to embryonal tumor induction by ethylnitrosourea in the opossum.

Opossums (Didelphis virginiana Kerr) exposed to 100 mg ENU/kg in single or incremental doses early in postnatal life developed a spectrum of epithelial and mesenchymal neoplasms including several types of embryonal neoplasms not previously induced in laboratory animals. A correlation was apparent to a varying degree between susceptibility to tumor induction and the state of morphologic maturation of the presumed target tissues at the light microscopic level for embryonal tumors of the eye, kidney, and brain. The susceptibility of the opossum eye to an ENU-induced intraocular teratoid medulloepithelioma extended over the period from 1 to between 3 and 4 weeks of age and was correlated with the differentiation of the apparent target cell, the nonpigmented ciliary epithelium of the pars ciliaris retinae. Induction of nephroblastomas was correlated with the presence in the kidney of stem cells (metanephric blastema) through the period from birth to between 6 and 8 weeks of age. Although susceptibility of the opossum brain to ENU induction of gangliogliomas was correlated with the state of differentiation of the germinal matrix from birth to 56 days of age, induction of these tumors was essentially limited to the 1st week postpartum. No definite correlation between vulnerability to tumor induction and tissue maturation was evident for a tumor of the jaw (ameloblastoma) with presumed origin from embryonic dental remnants. Our results indicated that the opossium early in postnatal life is a useful model for the induction and characterization of certain of the major dysontogenetic tumors, which have been difficult or impossible to reproduce in the traditional laboratory species.

Embryonal neoplasms in the opossum: a new model for solid tumors of infancy and childhood.

Opossums fed the chemical carcinogen ethyl nitrosourea early in postnatal life developed a variety of epithelial and mesenchymal embryonal neoplasms that were closely analogous, in morphology and biological behavior, to tumors of human infancy and childhood for which experimental models in laboratory animals are either imprecise or nonexistent. The embryonal tumors were found in association with, and occasionally at the same sites as, a limited number of malformations.