Increased ornithine decarboxylase (ODC) activity is associated with rapid cell proliferation in many cell types. The cellular effects of early weaning on intestinal development are not well established. To investigate whether ODC is involved in intestinal growth after early weaning, we precociously weaned suckling rats on postnatal d 15 and followed through d 21 (6 d after early weaning). Age-matched suckling pups served as controls. Rat pups were killed 1, 2, 3 and 6 d after early weaning and jejunal mucosa was assayed for ODC and sucrase activities, and protein and DNA contents. Jejunal cell proliferation was monitored by bromodeoxyuridine immunohistochemistry. Elevated jejunal ODC activity 1 d after early weaning was the earliest cellular event that was detected in the current study. ODC activity peaked at d 3 (about 15-fold greater than age-matched unweaned suckling controls). Sucrase activity was elevated at d 2 after weaning and peaked at d 3 (about 10-fold greater than controls). Greater bromodeoxyuridine immunostaining in early weaned rats occurred on d 3. Protein and DNA contents were greater in jejunal mucosa of early weaned rats at d 6. Serum corticosterone levels were elevated on d 1 and d 2 after early weaning compared to controls. To explore whether the intake of nonpurified diet played a role, we also compared the induction of jejunal ODC activity in early weaned pups and pups that were food-deprived for 1 d. ODC activity was not greater in the food-deprived group compared to suckling controls while the early weaned group had 6-fold greater activity 1 d after early weaning. Early weaning stimulates jejunal cell proliferation and differentiation. The temporal sequence of increased ODC activity followed by increases in other growth variables suggests that the induction of ODC activity may act as an early marker of intestinal growth during early weaning.

Small cell lung cancer (SCLC) manifests a range of phenotypes in culture that may be important in understanding its relationship to non-SCLCs and to tumor progression events in patients. Most SCLC-derived cell lines, termed "classic" SCLC lines, have properties similar to SCLC tumors in patients, including high expression of neuroendocrine markers and low c-myc oncogene expression. A significant number of SCLC lines characterized as "biochemical or morphologic variant" SCLC lines have decreased levels of endocrine differentiation markers associated with increased proliferative indices, amplification of the c-myc oncogene, and growth patterns and biochemical markers more typical of non-SCLCs. To delineate further the relationships between these phenotypes and the molecular events involved, we have inserted the v-Ha-ras gene in SCLC cell lines with (biochemical variant) and without (classic) an amplified c-myc gene. These two SCLC subtypes had markedly different phenotypic responses to similar levels of expression of v-Ha-ras RNA. No biochemical or morphologic changes were observed in classic SCLC cells. In contrast, in biochemical variant SCLC cells, v-Ha-ras expression induced features typical of large cell undifferentiated lung carcinoma, including adherent monolayer growth patterns, increased cloning efficiency, increased levels of non-SCLC cell markers, ultrastructural characteristics, and an acquired resistance to polyamine depletion typical of large cell carcinoma, but not SCLC, in vitro. Expression of v-Ha-ras in biochemical variant SCLC cells directly demonstrates that important transitions can occur between phenotypes of human lung cancer cells and that these may play a critical role in tumor progression events in patients. The finding provide a model system to study molecular events involved in tumor progression steps within a series of related tumor types.

We quantitated mRNA and protein for ornithine decarboxylase (ODC) and c-myc in formalin-fiied liver sections from 25 specimens of hepatocellular carcinoma (HCC) and seven normal livers by a non-radiolabeled in situ hybridization technique and immunohistochemistry. This non-radioactive in situ hybridization technique was highly specific, with virtually no background, and permitted quantitative analysis based on optical density. Reaction products were quantitated with computer-assisted microdensitometry. Samples were classified as normal, adjacent uninvolved, cirrhosis, welldifferentiated HCC, and poorly-differentiated HCC. There was a progressive increase in all four parameters measured, ODC mRNA and protein, and c-myc mRNA and protein, from normal, to adjacent uninvolved liver, to cirrhosis, to

Adenomatous colonic polyps constitute a precursor for colorectal cancer. Antibodies to these precancerous lesions might identify specific early tumor antigens. Adnab-9 is a murine monoclonal antibody raised against membranes of colonic adenomas. Adnab-9 binding in colonic washings (effluent) correlates with the presence of colorectal cancer. Immunohistochemical staining with Adnab-9 shows cytoplasmic reactivity in scattered cells in 4 of 31 adenomatous tissue sections, 0 of 14 sections of colorectal cancer cells, and 1 of 8 normal-appearing colonic mucosa specimens examined. Adnab-9 recognized a dominant M(r) 87,000 protein species in tissue extracts in the membrane-bound fraction of effluent by Western blotting. Adnab-9 binding by enzyme-linked immunosorbent assay in adenomatous extracts is higher than cancer or normal tissue, is membrane-bound, and is absent from established colorectal cancer cell lines. This distribution and nature of immunostaining suggest that Adnab-9 recognizes a determinant associated with the membrane component of a subpopulation of adenoma cells which may have a role in early colorectal neoplasia.