A remarkable overlap was observed between the gadd genes, a group of often coordinately expressed genes that are induced by genotoxic stress and certain other growth arrest signals, and the MyD genes, a set of myeloid differentiation primary response genes. The MyD116 gene was found to be the murine homolog of the hamster gadd34 gene, whereas MyD118 and gadd45 were found to represent two separate but closely related genes. Furthermore, gadd34/MyD116, gadd45, MyD118, and gadd153 encode acidic proteins with very similar and unusual charge characteristics; both this property and a similar pattern of induction are shared with mdm2, which, like gadd45, has been shown previously to be regulated by the tumor suppressor p53. Expression analysis revealed that they are distinguished from other growth arrest genes in that they are DNA damage inducible and suggests a role for these genes in growth arrest and apoptosis either coupled with or uncoupled from terminal differentiation. Evidence is also presented for coordinate induction in vivo by stress. The use of a short-term transfection assay, in which expression vectors for one or a combination of these gadd/MyD genes were transfected with a selectable marker into several different human tumor cell lines, provided direct evidence for the growth-inhibitory functions of the products of these genes and their ability to synergistically suppress growth. Taken together, these observations indicate that these genes define a novel class of mammalian genes encoding acidic proteins involved in the control of cellular growth.

EMBL accession no. X51829 cDNA clones of myeloid differentiation primary response (MyD) genes activated in the absence of protein sysnthesis in M1 myeloblastic leukemia cells induced for terminal differentiation by IL6, have been isolated (1). Here we report the full length nucleotide and deduced amino-acid sequences of MyDi 16, a novel MyD gene, which exhibits biphasic kinetics of expression, with an early peak (1 hr) and a decline followed by increased levels of steady state mRNA in terminally differentiated Ml cells (1). MyD 116 expression was observed also in murine bonemarrow, but not in non-myeloid tissues (1). MyD1 16 encodes for a 2.5 kb mRNA, having a very short 3' untranslated region with multiple AT3 motifs (underlined), implicated in mRNA destabilization (2). The MyDi 16 encoded protein (657aa) harbors 419 almost perfect 38aa long repeats (underlined), each containing a PEST region, characteristic of short lived proteins (3). The MyDi 16 protein does not contain protein secretory signals, transmembrane domains or known protein-DNA binding motifs; it contains, however, potential protein kinase phosphorylation sites (position 4, 181), amidation site (position 653), and 19 casein kinase II phosphorylation sites, including 3 in each repeat.

The proto-oncogenes c-jun, junB, junD, and c-fos recently have been shown to encode for transcription factors with a leucine zipper that mediates dimerization to constitute active transcription factors; juns were shown to dimerize with each other and with c-fos, whereasfos was shown to dimerize only with juns. Growth and differentiation of animal cells is a wellcontrolled and highly conserved process involving multiple changes in gene expression that are developmentally regulated and result in the conversion of proliferating, undifferentiated cells into nonproliferating, highly specialized cells. A profound example of this process, which continues throughout life, is the complex blood cell formation, whereby a hierarchy of hematopoietic progenitor cells in the bone marrow proliferate and differentiate along multiple, distinct cell lineages, including the proliferation and differentiation of myeloid precursor cells into mature granulocytes and macrophages (57). The establishment of in vitro culture systems for the clonal development of bone marrow cells (6,43) and the availability of Ml myeloblastic leukemia cells, which proliferate autonomously and can be induced for differentiation and loss of leukemogenicity by physiological myelopoietic factors (15,47,49), provide an excellent biological system with which to study, side by side, the molecular biology of normal blood cell development and lesions that afflict it in leukemia and upon its progression (20,23,29,30).To enhance our understanding of the regulation of normal terminal differentiation and alterations in these regulatory processes that block differentiation, leading to leukemogenicity and its progression, recently we isolated and charac-

The uptake of pesticides by earthworms from aqueous solutions was examined and shown to be a reversible physical process. Measurements of distributions of pesticides between aqueous solutions and worm solids showed that adsorption coefficients were related to octanol‐water distribution coefficients, as are soil‐water distributions. From these relationships it was calculated that concentration factors of stable chemicals in earthworms from soil should be similar, except for polar substances which penetrate poorly, and be determined mainly by the soil organic matter content. Examination of uptake from soils indicated that the calculated concentration factors are unlikely to be achieved because of slow diffusion of chemicals in soils and because of metabolism in the soil or the worm.

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