Renal tumors were produced by injection of a cell fraction of a tumor into triploid tadpoles of Rana pipiens before they began feeding. Triploid tumor cells were dissociated and transplanted into activated and enucleated eggs. Pluripotency of the implanted nuclei was evidenced by the formation of swimming triploid tadpoles.

The sequences of two frog herpesviruses, Ranid herpesvirus 1 and Ranid herpesvirus 2, were determined. They are respectively 220 859 and 231 801 bp in size and contain 132 and 147 predicted genes. The genomes are related most closely in the central regions, where 40 genes are conserved convincingly. Nineteen of these genes are also conserved in a fish herpesvirus, Ictalurid herpesvirus 1. The terminal regions of the genomes are largely not conserved and contain many of the 15 families of related genes present in each genome. The frog herpesviruses are unique among sequenced herpesviruses in that the three exons of the gene encoding the putative ATPase subunit of terminase are not specified by the same DNA strand and in that they encode a putative DNA (cytosine-5-)-methyltransferase and have extensively methylated genomes.

Diploid frog nuclei from differentiated somatic cells, transplanted into enucleated eggs to determine whether cell specialization generally involves irreversible genetic changes, have shown that nuclei from specialized somatic cells still contain the genes specifying the cell types and organ systems of swimming tadpoles. However, those tadpoles failed to feed and did not survive beyond the initial tadpole stages. Here we report that, after incubation in oocytes, triploid erythrocyte nuclei from juvenile frogs of Rana pipwns directed the formation of feeding tadpoles that survived up to a month and had differentiated hind limb buds. These tadpoles occurred at a high yield and showed the most extensive development so far obtained from documented differentiated somatic nuclei.Whether or not cell specialization generally involves irreversible genetic changes has not been determined. In principle, DNA losses would be irreversible, but at the present time these losses occur as a regular event in only a few species, e.g., in some protozoans, nematodes, and insects (1), as well as in the genetic rearrangement of mammalian immunoglobulin genes (2). However, it has not yet been shown that nuclei of specialized somatic cell types are genetically totipotent.A rigorous test of the gene content in cells is to transfer a living nucleus into an enucleated egg and allow development to proceed. The extent of development and differentiation that ensues reveals the gene content present in the transplanted nucleus. Such experiments were performed originally with early embryonic nuclei in the anuran amphibian Rana pipiens (3, 4) and later extended to other species (reviewed in refs. 5-8). Since normal adults developed, these results signified that all the genes required for normal development are present and functional in young embryonic nuclei.In later years numerous heroic attempts were made to test the developmental potential of frog nuclei from specialized somatic tissues of Xenopus laevis. Three metamorphosed frogs were obtained from nuclei ofcells cultured from minced hatching tadpoles (9). Also one metamorphosed (10) and two fertile frogs (11) were derived from nuclei of larval intestine. However, the interpretation of these results remained equivocal, because the technical procedures at that time precluded distinction between undifferentiated stem cells and differentiated cells in the tissues employed. Later, procedures became available for estimating the purity of the donor cell population, and evidence has now been accumulated that some specialized diploid somatic nuclei can direct the formation of swimming tadpoles. These cases include adult nuclei from Xenopus skin (12), spleen cells (13), and embryonic myotome cells tested in eggs (14), as well as adult erythrocyte nuclei tested in Rana oocytes (15). In all these cases, the nuclear transplant tadpoles constructed the various organ systems, tissues, and cell types normally found in tadpoles, thus demonstrating the important conclusion that at least some of the tes...

This is a revised and updated edition of a text used in undergraduate courses on cancer biology. It covers everything from the molecular basis of cancer to clinical aspects of the subject, and has a lengthy bibliography designed to assist newcomers with the cancer literature. An introduction acquaints students with the biological principles of cancer and the human dimensions of the disease by considering genuine cases of cancer in fictionalized letters. Other chapters discuss cancer pathology, metastasis, carcinogenesis, genetics, oncogenes and tumor suppressors, epidemiology, and the biological basis of cancer treatment. Also included are an appendix with descriptions of common forms of cancer, a glossary of cancer-related terms and colour plates to illustrate the pathology of many of the types of cancer discussed in the text. Upper-division undergraduates with a background in freshman biology and chemistry, as well as beginning graduate students will find this a valuable text.

Ranid herpesvirus 1 (RaHV-1) is the etiological agent of the Lucké renal adenocarcinoma of the North American leopard frog Rana pipiens. Construction of cosmid libraries containing RaHV-1 DNA inserts allowed the derivation of a BamHI map for the viral genome. Summation of fragment sizes indicates that the genome is 217 kbp in size, a value in accordance with the most recent published estimate (220 kbp) obtained by field-inversion gel electrophoresis. The DNA sequence of the 39,757-bp insert in 1 cosmid (cos54) was determined and was predicted to contain 21 complete and 3 partial genes. In all, 12 genes have distant counterparts in a fish herpesvirus (ictalurid herpesvirus 1) and are present in 2 blocks, 1 of which is relatively inverted. This indicates that RaHV-1 belongs to the fish virus lineage of the herpesvirus family rather than to the lineage populated by mammalian and avian viruses. The remaining 12 genes in cos54 lack counterparts in any other herpesvirus. One of these encodes a putative DNA (cytosine-5) methyltransferase. This raises the possibility that biological processes induced in the host by RaHV-1 might involve methylation of cellular DNA by the viral enzyme.