Norio Hirota

Heme-biosynthetic enzyme activities and porphyrin accumulation in normal liver and hepatoma cell lines of rat.

The activities of four heme-biosynthetic enzymes, δ-aminolevulinic acid (ALA) synthase, ALA dehydratase, porphobilogen (PBG) dearninase, and ferrochelatase, were studied in five epithelial cell lines of normal rat liver origin (Re, REC-10, RLC-24, M, Culb-TC) and five cell lines derived from Yoshida ascites hepatoma (JTC-1, JTC-2, JTC-15, JTC-16, JTC-24). The JTC series of hepatoma-derived cell lines exhibited decreased ALA synthase activity and increased ALA dehydratase activity, although the activities of all four enzymes and the Km values for their respective substrates varied widely from one cell line to another, a finding suggesting that specific regulatory mechanisms for porphyrin metabolism might operate in each cell type. M cells, which were transformed by 4-dimethylaminoazobenzene in vitro, gave the most abnormal Km values of heme-biosynthetic enzymes among all the cell lines studies, and were found to accumu2ate hematoporphyrin derivative (HpD).

Effect of DNA synthesis on induction of preneoplastic and neoplastic lesions in rat liver by a single dose of methylazoxymethanol acetate

A single intravenous injection of methylazoxymethanol (MAM) acetate in doses of either 20 or 35 mg/kg body weight to male Sprague-Dawley rats induced altered liver cell foci and later, liver neoplasms in a dose related manner. Sequential observations in the rats given 35 mg/kg and thereafter fed an iron-loading diet revealed that the number of iron-excluding foci/cm2 increased with time. Partial hepatectomy (PH) before the high dose of MAM acetate resulted in 100% lethality while hepatectomy before the low dose carcinogen exposure lead to a higher incidence of neoplasms than in rats that received carcinogen alone. PH after either high or low dose carcinogen exposure did not result in a greater occurrence of liver neoplasms.

Liver-like alkaline phosphatase in the tissue-unspecific type enzyme found in rabbit organs

Rabbit liver and kidney tissues are known to produce an intestinal-like alkaline phosphatase (IAP-like enzyme) as a dominant isozyme, with a minor isozyme of tissue-unspecific type (UAP), unlike humans and other mammalians. We investigated immunohistochemically and biochemically these unique isozymes in the rabbit liver and bone, and compared them with the human isozyme. In rabbit liver, UAP was found to be localized only in the apical part of the membrane of cells lining the bile duct, whereas IAP-like enzyme was found in the sinusoidal membrane of hepatocytes. Rabbit liver UAP was separated from IAP-like enzyme by DEAE-cellulose column chromatography. Rabbit bone tissue contained only one UAP isozyme. The two UAPs were biochemically and physicochemically compared with human liver AP. Both UAPs reacted with an anti-human liver AP monoclonal antibody, not with an anti-human bone AP monoclonal antibody, indicating that both enzymes have the same antigenicity as human liver AP. Rabbit liver and bone UAPs had similar N-linked sugar-chain heterogeneities to the respective human enzymes. In addition, rabbit bone AP also had an O-linked sugar chain, as did human bone AP, unlike rabbit and human liver APs.

COMPARATIVE STUDY OF ABNORMALITY IN GLYCOGEN STORING CAPACITY AND OTHER HISTOCHEMICAL PHENOTYPIC CHANGES IN CARCINOGEN-INDUCED HEPATOCELLULAR PRENEOPLASTIC LESIONS IN RATS

A sequential comparison was made between abnormal glycogen storage and other histochemical phenotypic changes in hepatocellular precancerous lesions (altered foci and neoplastic nodules) during various stages in the process of development of cancer in rat liver. N‐2‐fluorenylacetamide was fed to male rats for 8 weeks and groups of rats were killed at the end of carcinogen feeding and at 12 and 24 weeks on control diet. Foci rich in glycogen storage accounted for a majority of all foci over the course of experiment, while foci devoid of glycogen storage, which were absent at the end of carcinogen feeding, gradually increased in number during maintenance. Glycogen‐deficient lesions that might appear to arise from glycogen‐rich lesions displayed hyper‐basophilia demonstrated by toluidine blue reaction, but often lacked gamma‐glutamyl transpeptidase activity. Resistance to iron accumulation was consistently shown in all precursor lesions for hepatocellular carcinoma in the siderotic liver regardless of abundance or absence of cellular glycogen. It was suggested that properties such as loss of glycogen storing capacity, hyperbaso‐philia, and some cellular atypicality resembling those of carcinoma cells might be essential elements for malignant progression.

A New Method for Measuring the Speed of Sound in Rat Liver ex Vivo Using an Ultrasound System: Correlation of Sound Speed with Fat Deposition

The speed of sound correlates well with the fat content of the liver. Therefore, non-invasive quantification of sound speed in the liver might be of diagnostic value. Here we describe a new non-invasive method that would be clinically applicable for measurement of sound speed in the liver. Sprague-Dawley rats were divided into two groups: a control group and a fatty liver group prepared by keeping the rats on a choline-deficient diet for 6 wk. The livers were subjected to pathologic and biochemical analysis; the speed of sound through the liver tissue was measured using our proposed method and a pulser-receiver as standard. Our results indicated that use of the proposed method makes it feasible to diagnose fatty liver with good accuracy on the basis of sound speed. This approach would have considerable potential for non-invasive diagnosis of fatty liver and would be a valuable adjunct to conventional liver diagnostic procedures.

Comparative tumor initiating activity of 10-methylbenzo[a]pyrene, 7,10-dimethylbenzo[a]pyrene and benzo[a]pyrene*

The tumor initiating activity on mouse skin of benzo[a]pyrene (BaP), 7,10-dimethylBaP, and 10-methylBaP was determined. Each compound was tested at initiating doses of 50 microgram and 100 microgram with promotion by application 3 times weekly of 2.5 microgram tetradecanoylphorbol acetate. BaP induced tumors in 40% (100 microgram) and 25% (50 microgram) of the animals. No tumors were observed in either group treated with 7,10-dimethylBaP. In the groups treated with 10-methyl-Bap, the incidence of tumor bearing animals was 20% at both doses. These results and the results of previous studies on other methylated BaP derivatives suggest that the mechanism of activation of these compounds is similar to that observed for the parent hydrocarbon and probably involves formation of an angular ring diol-epoxide or epoxide.

Case Report: A Variant Alkaline Phosphatase-Producing Gastric Carcinoma with Super Bone Scan

in English) 4. Uchida T, Shikata T, Shimizu S, Takimoto Y, Iino S, Suzuki H, Oda T, Hirano K, Sugiura M: Gonadotropin and alkaline phosphatase producing occult gastric carcinoma with widespread metastasis of generalized bone. Cancer 48:140 ± 150,

Histochemical, ultracytochemical and biochemical study of alkaline phosphatase activity during gastric carcinogenesis.

In our recent study of carcinogenic action of N-methyl-N-nitrosourea (MNU) in drinking water on the rat stomach, we found not only selective induction of glandular stomach carcinoma in high incidence but also occasional ossification within the stroma of cancer [l]. These findings led us to become much interest in stromal changes which might possibly precede and be related to ossification in the process of gastric carcinogenesis by MNU. It has been suggested by Robinson [2] and Cartier [3] that mechanisms of ossifying process in the stroma is enzymatic and that alkaline phosphatase (ALP) is one of the most important enzymes which might play a role in the process. The purpose of the present study was to demonstrate the localization of ALP by histochemistry and ultracytochemistry and to biochemically analyze ALP isozymes in MNU-induced neoplastic stomach lesions of rats and their sera. Bone turnover markers in the sera were also biochemically assayed. Herein, we report a marked enhancement of tissue-unspecific ALP production in the stroma of adenocarcinomas of the stomach in a rat model of gastric carcinogenesis with occasional heterotopic ossification, and discuss some significance of the enhanced ALP activity during MNU-induced gastric carcinogenesis.

Clinicopathological study on cystadenocarcinoma of the pancreas

SummaryAlthough rare, mucinous cystadenocarcinoma of the pancreas is an established pathological entity. However, its characteristic features on diagnostic imaging have not yet been defined. Based upon clinicopathological studies on 5 cases, two subgroups of mucinous cystadenocarcinoma of the pancreas are proposed: the endophytic and the exophytic types.The former consist of large well-demarcated cystic tumors with numerous inward-growing cauliflower-like excrescences in mucinous material, which were characteristically demonstrated either by CT or ultrasonography. Tumors of this subtype were visualized as hypervascular masses in the capillary phase of angiography. Areas of malignant tissue were well-demarcated without capsular invasion, and tumors were free from lymph node or distant metastasis.Though cystic, the exophytic subtype had negligible inward-growing papillary projections. Corresponding to their macroscopic features, these tumors were demonstrated as cystic lesions lacking papillary projections on ultrasonography or CT. No tumor stains could be demonstrated by angiography. Despite of their smaller size than the former subtype, cancerous growth penetrated through the cyst wall and metastasized to lymph nodes, causing poorer prognosis than in the former.

Intranuclear rodlets in undifferentiated carcinomas of salivary glands in strain A mice in a study involving a tobacco specific nitrosamine, N-nitrosonornicotine.

Undifferentiated carcinomas of the salivary glands were found in 2 of 44 (4.5%) strain A mice injected intraperitoneally with a tobacco specific nitrosamine, N-nitrosonornicotine (NNN). The presence of intranuclear rodlets (INR) in the salivary carcinomas provided the first demonstration of such structures in a non-neuronal tumor in mice. Two types of rodlets were exhibited; one was composed of fibrillar filaments arranged in bundles, and the other was much thicker, branching in form. These INR appeared to be closely associated with nuclear chromatin or nucleoli.