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Structural analysis of 55 nearly full-length cDNA clones revealed heterogeneity in the 5'-untranslated regions of rat liver alkaline phosphatase mRNAs. The 5' extremities diverged into two totally unrelated sequence stretches at the position 88 nucleotides upstream of the initiation codon ATG. These two sequences, referred to as E1 and E2, were assigned on the genome about 36 000 base pairs (36 kbp) and 10 kbp upstream, respectively, of the exon coding for the 5'-most part of the common region. The gene consisted of 13 exons, including E1 and E2, and spanned about 56 kbp. The 11 exons (E3 to E13) following E1 and E2 were shared in common by the El-type and the E2-type mRNAs. Analyses by SI nuclease mapping and primer extension revealed the presence of two independent transcription-initiation sites specific to each of the El and E2 sequences. These results are interpreted as indicating a possible alternative usage of two leader exons, hence the presence of two independent promoters. Structural features of these putative promoters are described in the context of transcriptional fundamental and regulatory cis-elements. [ABSTRACT FROM AUTHOR]

The insulin-like growth factor II (rlGFll) is a mitogenic polypeptide, the expression of which is high in most rat tissues during embryonic development, yet is barely detectable in adult tissues except for some of neurogenic origin. The gene is present as a single copy in the genome but has three alternative leader exons, E1, E2 and E3, thereby with three independent transcriptional promoters. We analysed the expression of rIGFII and the relative efficiency of each promoter in hepatocarcinogen-treated livers, primary hepatomas and established hepatoma lines. The E3-specific product was first detected after 6 weeks of 3'-methyl-4-dimethylaminoazobenzene treatment and those of E1 and E2 also after 9 weeks. The levels gradually increased according to the sum of the treatment period, but reactivation was nil in the regenerating liver. Consistently high levels of expression were observed in all primary tumors, but the relative promoter activity varied with the tumor. The significance of rIGFII reactivation was discussed in the light of the hepatocarcinogenesis. [ABSTRACT FROM PUBLISHER]

1,3-Di(4-sulfamoylphenyI)-triazene (DSPT), synthesized from two equivalents of sulfanylamide and one equivalent of sodium nitrite, induced specific types of tumors (lympho-reticular neoplasias) in the offspring, when it was given orally to pregnant mice on Days 13–18. Tumor incidences were 6.1, 20.0, and 21.7%, when DSPT was given at 1, 4 and 10% concentration in the diet, respectively, while the control value was 0.8%. DSPT did not induce lung tumors, which are commonly induced by mutagenic carcinogens. DSPT also produced malformations (cleft palate, exencephalus, etc.), when given intraperitoneally on Days 9, 10 and 11. Incidence increased with increasing doses of DSPT, that is, 15.8, 21.1 and 36.7% at doses of 22, 36 and 44 μg/g, respectively, while the incidence was 0.3% in the untreated controls. DSPT was found to be non-mutagenic but weakly clastogenic in . [ABSTRACT FROM PUBLISHER]