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Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 1,693 records · Page 94Linked to original sources
PubMed1981

Failure of C3H mice to develop lung granuloma after intravenous injection of BCG cell wall vaccine. Demonstration of a defect in lymphoid cells.

C57Bl/6 (B6) mice produced highly developed granulomata in the lung 3 or 4 weeks after intravenous injection with oil-associated BCG cell walls (CW), but C3H/He (C3H) mice did not. The potential to develop granulomata is genetically controlled (Yamamoto & Kakinuma, 1978). It is probable that the genes control only T-cell mediated granuloma and not non-specific inflammation prior to onset of immunopathological response. The retention of an FITC-labelled BCG CW preparation in the lungs of B6 and C3H mice did not differ until 10 days after injection, although 24 hr uptake of 125 I-labelled BCG CW in B6 lung was twice as much as that in C3H lung. Furthermore, C3H mice did not show a secondary type granuloma response in the lungs after subsequent injections of BCG CW. In experiments using radiation chimaeras, B6 mice reconstituted with C3H bone marrow cells were unable to produce a granulomatous response to BCG CW. In contrast, C3H mice reconstituted with B6 bone marrow cells showed a good granulomatous response. These results suggest that the C3H mice possessed a deficiency within their lympho-haematopoietic cells.

Animals↗
PubMed1981

Metabolic fate of N-butyl-N-(4-hydroxybutyl)nitrosamine homologs in the rat, in relation to their organotropic carcinogenicity to the urinary bladder.

The metabolic fate of alkyl homologs (alkyl=methyl, ethyl, propyl, pentyl, and tert-butyl) of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), a potent bladder carcinogen, was investigated in the rat, in order to elucidate any possible correlation of structure and metabolism with organospecific carcinogenicity to the urinary bladder of these N-nitrosamines. They were extensively metabolized in the rat, no unchanged compounds being found in the urine. The metabolic pattern of these alkyl homologs of BBN was essentially similar to that of BBN. Their principal urinary metabolite was the corresponding N-alkyl-N-(3-carboxypropyl)nitrosamine except in the case of the pentyl homolog. Minor metabolites characterized were subsequent transformation products of the principal metabolite by beta-oxidation according to the Knoop mechanism (i.e., N-alkyl-N-(2-hydroxy-3-carboxypropyl)nitrosamine, N-alkyl-N-(carboxymethyl)nitrosamine and N-alkyl-N-(2-oxopropyl)nitrosamine) and the glucuronic acid conjugate excretion of the N-alkyl-N-(c-carboxypropyl)nitrosamine with selective induction of bladder cancer by the N-alkyl-N-(4-hydroxybutyl)nitrosamine in rats is discussed.

Animals↗
PubMed1981

Metabolic fate of N-alkyl-N-(3-hydroxypropyl and 2-hydroxy-ethyl)nitrosamines in the rat in relation to the induction of bladder cancer by N-butyl-N-(4-hydroxybutyl)nitrosamine and its homologs.

The metabolic fate of N-alkyl-N-(3-hydroxypropyl)nitrosamines and N-alkyl-N-(2-hydroxyethyl)nitrosamines (alkyl=butyl, ethyl) [analogs of N-alkyl-N-(4-hydroxybutyl)nitrosamines, which are potent bladder carcinogens] was investigated in the rat in order to elucidate a possible relationship between chemical structure, in vivo metabolism, and organotropic carcinogenicity to the urinary bladder of N-alkyl-N-(4-hydroxybutyl)nitrosamines. The principal urinary metabolites of N-alkyl-N-(3-hydroxypropyl)nitrosamines and N-alkyl-N-(2-hydroxyethyl)nitrosamines, which are not carcinogenic to the urinary bladder but are hepato-carcinogenic in rats, were the corresponding 2-carboxyethyl and carboxymethyl compounds. Urinary metabolites with a 2-carboxyethyl or carboxymethyl group are not important, as far as the induction of bladder cancer is concerned, and the urinary excretion of metabolites having a 3-carboxypropyl chain is essential for the induction of bladder cancer.

Animals↗
PubMed1981

Mutagenicity of N-alkyl-N-(alpha-acetoxyalkyl) nitrosamines in V79 Chinese hamster cells in relation to alkylating activity.

Mutation to ouabain resistance and cytotoxicity were tested in V79 Chinese hamster cells after the cells had been treated for 2.5 hr with a series of N,N-dialkylnitrosamines (alkyl=methyl, ethyl, propyl, butyl or tert-butyl) monosubstituted at the alpha-carbon with an acetoxy group. The effects of the length of alkyl chain and the mode of substitution with the acetoxy group on the cytotoxicity and mutagenicity were examined. In the series of N-alkyl-N-(acetoxy-methyl) nitrosamines with an acetoxy group at the primary alpha-carbon, the methylating compound N-methyl-N-(acetoxymethyl) nitrosamine was the most cytotoxic and mutagenic, and the biological activities decreased in the order of ethyl, butyl and propyl homologs. N-tert-Butyl-N-(acetoxymethyl) nitrosamine was not mutagenic at the concentration tested. At equitoxic concentrations, N-ethyl-N-(acetoxymethyl) nitrosamine was found to be the most mutagenic. Of the two N-alkyl-N-(alpha-acetoxybutyl) nitrosamines having an acetoxy group at the secondary alpha-carbon, N-methyl-N-(alpha-acetoxybutyl) nitrosamine was more cytotoxic and mutagenic than N-butyl-N-(alpha acetoxybutyl) nitrosamine. A comparison of the corresponding N-alkyl-N-(acetoxymethyl) nitrosamines and N-alkyl-N-(alpha-acetoxybutyl) nitrosamines showed that the latter had stronger activities. A plot of the mutation frequency versus the ability of the alpha-acetoxy compounds to alkylate 4-(p-nitrobenzyl) pyridine was linear. This indicates that the chemical reactivity of the compounds plays an important role in inducing mutation in V79 Chinese hamster cells.

Alkylating Agents↗
PubMed1981

Metabolic fate and carcinogenicity of N-(omega-hydroxyalkyl) N-(4-hydroxybutyl) nitrosamines analogs of N-butyl-N-(4-hydroxy-butyl) nitrosamine, in the rat.

The metabolic fate and carcinogenicity fo three omega-hydroxy derivatives of N-alkyl-N-(4-hydroxybutyl) nitrosamines, potent bladder carcinogens, were investigated in the rat. They were N-(2-hydroxyethyl)-N-(4-hydroxybutyl)-nitrosamine (HEHBN), N-(3-hydroxypropyl)-N-(4-hydroxybutyl) nitrosamine (HPHBN), and N-N-bis(4-hydroxybutyl) nitrosamine (BHBN). The principal urinary metabolite of HEHBN as well as HPHBN was identified as the corresponding 3-carboxypropyl compound, while the main metabolite of BHBN was N,N-bis (3-carboxypropyl) nitrosamine, indicating the preferential metabolic oxidation of the 4-hydroxybutyl chain to the 3-carboxypropyl group in the N-(omega-hydroxyalkyl)-N-(4-hydroxybutyl) nitrosamines. All three N-nitrosamines having the 4-hydroxybutyl chain induced neither bladder tumor nor any tumor in other organs under conditions similar to those used for N-alkyl-N-(4-hydroxy-butyl) nitrosamines. The essential structural and metabolic requirements in N-nitrosamines for the induction of bladder cancer in the rat are discussed.

Animals↗
PubMed1981

Metabolic fate of N-butyl-N-(4-hydroxybutyl) nitrosamine and N, N-dibutylnitrosamine in the guinea pig, with reference to their carcinogenic effects on the urinary bladder.

The metabolic fate of two urinary bladder carcinogens, N-butyl-N-(4-hydroxy-butyl) nitrosamine (BBN) and N-N-dibutylnitrosamine (DBN), was studied in the guinea pig, in order to elucidate species differences of response to these N-nitrosamines in this animal species and the rat. Based on the urinary metabolites characterized after oral administration of these compounds, the metabolic pathways of BBN and DBN in the guinea pig were shown to be essentially similar to those in the rat. The principal urinary metabolite of BBN and DBN in the guinea pig, however, was not N-butyl-N-(3-carboxypropyl) nitrosamine (BCPN), as was the case in the rat, but the glucuronic acid conjugate of BBN and that of N-butyl-N-(3-hydroxybutyl) nitrosamine, respectively. The species variation in response to BBN and DBN as bladder carcinogens in these animals is discussed on the basis of the urinary excretion of BCPN.

Animals↗
PubMed1981

Metabolic fate of N, N-dipropylnitrosamine and N, N-diamylnitrosamine in the rat, in relation to their lack of carcinogenic effect on the urinary bladder.

The metabolic fate of N, N-dipropylnitrosamine (DPN) and N, N-dipentyl-(=diamyl) nitrosamine (DAN), which induced tumors principally in the liver and esophagus but not in the urinary bladder, was studied in the rat, in order to elucidate the reason for this lack of carcinogenicity to the urinary bladder in contrast with the butyl homolog, N, N-dibutylnitrosamine (DBN), a potent bladder carcinogen. The principal urinary metabolite of DPN was identified as the omega-oxidation product N-propyl-N-(2-carboxyethyl) nitrosamine. The (omega-1)-oxidation product N-propyl-N-(2-hydroxypropyl) nitrosamine and its glucuronic acid conjugate were also characterized as metabolites. The principal urinary metabolite of DAN was N-amyl-N-(2-carboxyethyl) nitrosamine, which was formed by metabolic shortening of the amyl chain by omega- and beta-oxidations according to the Knoop mechanism. Besides this, seven compounds oxidized at omega-, (omega-1)-, (omega-2)-, and (omega-3)- positions of one or both amyl chains were isolated and characterized, some of which were shown to be also present as the corresponding glucuronide. The metabolic pattern of DPN and DAN was compared with that of DBN, and the lack of carcinogenicity of the former N-nitrosamines to the urinary bladder of rats is discussed on the basis of their urinary metabolites.

Animals↗