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Polyadenylated RNAs of certain human tumour cell lines are shown to contain transcripts related to the cell-derived transforming onc genes of molecularly cloned primate, murine or avian transforming retrovirus genomes. Thus, analogues of retroviral transforming genes are both present and frequently expressed in human neoplastic cells.

The transforming gene of a human lung carcinoma-derived cell line, Hs242, has been cloned in biologically active form, and identified as c-bas/has (otherwise known as c-Ha-ras). The genetic lesion responsible for the transforming activity of the Hs242 oncogene has been localized to a point mutation in the second exon which results in the substitution of leucine for glutamine as amino acid 61 of the predicted protein. No changes were observed in the first exon, the region of c-bas/has in which a point mutation is responsible for activation of the T24 and EJ bladder carcinoma oncogenes.

The genetic change that leads to the activation of the oncogene in T24 human bladder carcinoma cells is shown to be a single point mutation of guanosine into thymidine. This substitution results in the incorporation of valine instead of glycine as the twelfth amino acid residue of the T24 oncogene-encoded p21 protein. Thus, a single amino acid substitution appears to be sufficient to confer transforming properties on the gene product of the T24 human bladder carcinoma oncogene.

SEMINAL PLASMA—the fluid in which spermatozoa are ejaculated—has been known to inhibit reversibly both RNA and protein synthesis in sperm cells1–3. Here we report the isolation from seminal plasma, purification to homogeneity, and characterisation of a protein which we have called ‘seminalplasmin’, that specifically inhibits rRNA synthesis in Escherichia coli and is highly antimicrobial.

SEMINALPLASMIN, a protein isolated from bovine seminal plasma, specifically and almost completely inhibits synthesis of rRNA in whole Escherichia coli cells at extracellular concentrations lower than those needed for bacteriocidal action of many established antibacterial agents1. We show here that seminalplasmin also strongly inhibits the transcription of various natural and synthetic templates by E. coli RNA polymerase in vitro, and that it does so by binding strongly to the polymerase. Seminalplasmin is, to our knowledge, the first protein isolated from an eukaryote to inhibit RNA polymerase. There is, however, a protein synthesised in E. coli following a phage infection and coded by the phage genome, which appears to inhibit E. coli RNA polymerase2.

Avian myeloblastosis virus (AMV), like other acute transforming viruses, arose by recombination between its helper virus and host cellular sequences. The latter sequences, termed v-myb, are responsible for the oncogenic properties of the virus. AMY causes acute myeloblastic leukaemia in chickens and transforms a specific class of haematopoietic cells in vitro, but does not induce morphological transformation of cultured fibroblasts, suggesting that only a restricted target-cell population is responsive to its transforming gene product1,2. The normal cellular counterpart of v-myb, c-myb, is highly conserved and is present in all vertebrate and some invertebrate species examined3,4. DNA rearrangements and altered expression of the myb oncogene have been reported in mouse lymphoid tumours5–7and human myeloid8and colon tumours9. The mechanism of activation of the cellular proto-oncogenes is thought to involve the structural alteration of the coding regions that result in either the synthesis of an altered gene product or the enhanced expression of a proto-oncogene caused by alterations in its regulatory elements. To distinguish between these two mechanisms, we have cloned and sequenced the chicken c-myb complementary DNA and compared it with that of v-myb sequences. We demonstrate that during the transduction of the cellular sequences and/or viral passage a substantial portion of the coding region of the c-myb gene has been lost from both the 5′ and 3′ ends, resulting in the generation of a truncated gene product that mediates the transforming function of the virus.

There are only four positions in the amino acid sequences of immunoglobulin variable region domains of all species at which the same amino acid is always found1. The compiled sequences of rabbit heavy chain variable (VH) domains have 48 invariant positions1,2and at 14 additional positions in the first and third framework segments the different amino acids found correlate with the rabbits' VHa allotype3–5. This VHallotypic system with three common ‘alleles’ VHa1, VHa2 and VHa3 inherited in simple mendelian fashion3,4poses the question of how gene families with distinct sets of conserved codons have evolved and been maintained in the midst of information leading to hypervariability. Here we report a cDNA sequence that encodes a protein characteristic of the rabbit VHa2 allotype and we predict the allotype-associated codons that may be found in VHa1 and VHa3 genes. We have also found within the second hypervariable, complementarity-determining region (CDR2) encoded by our cDNA clone, a DNA sequence highly homologous to a human DHminigene6. This observation and a similar one of Wu and Kabat7, who identified a DHminigene sequence in the CDR2 of a cloned human VHgene8, lends support to their idea that D minigene information has contributed to CDR2 either during evolution or ontogeny7. Gene conversion9,10, minigene assortment11,12or insertion13mechanisms may be involved both in the generation of hypervariability and the conservation of allotype codons.