Selektive Erzeugung von Blasenkrebs an Ratten durch Dibutyl- und N-Butyl-N-butanol(4)-nitrosamin

Druckrey, H.; Preußmann, R.; Ivanković, S.; Schmidt, Christian; Mennel, H. D.; Stahl, K. W.

doi:10.1007/bf00524156

Cited by 142 publications

(45 citation statements)

References 13 publications

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“…Liver tumours have been reported in the rat (Druckrey et al, 1962(Druckrey et al, , 1964, guinea pig (Ivankovic and Bucheler, 1968) and ICR mouse (Takayama and Imaizumi, 1969) but were not observed in the present experiments. Conversely bladder tumours were not found in the male ICR mouse but occur with high frequency in the male C57BL/6 mouse; a strain with a very low spontaneous tumour incidence.…”

Section: Discussioncontrasting

confidence: 61%

“…While N-hydroxylation could occur with DBN to produce a reactive hydroxylamine derivative (Heath, 1962) it is more likely that C-hydroxylation occurs, possibly followed by conjugation, to produce a hydrophilic compound which is not reabsorbed by the renal tubules and which could yield a reactive intermediate, either spontaneously or enzymatically, in the bladder. Druckrey et al (1964) favour this as the most probable sequence of events leading to the excretion of a urinary carcinogen, and have demonstrated in the urine of treated rats the presence of several polar metabolites of DBN in which the nitroso group is intact. Although these metabolites have not been identified they have shown that butyl-4-hydroxybutylnitrosamine is a potent carcinogen acting solely on the bladder (Druckrey et al, 1964).…”

Section: Discussionmentioning

confidence: 94%

“…Druckrey et al (1964) favour this as the most probable sequence of events leading to the excretion of a urinary carcinogen, and have demonstrated in the urine of treated rats the presence of several polar metabolites of DBN in which the nitroso group is intact. Although these metabolites have not been identified they have shown that butyl-4-hydroxybutylnitrosamine is a potent carcinogen acting solely on the bladder (Druckrey et al, 1964). The exact nature of the reactive intermediate in nitrosamine carcinogenesis is currently the subject of intensive investigation.…”

Section: Discussionmentioning

confidence: 94%

“…The dialkyl nitrosamines predominantly produce tumours of the liver, lung, oesophagus, kidney, stomach, nasal sinus and bronchus. Dibutylnitrosamine (DBN) and its hydroxylated derivative butyl-4-hydroxybutylnitrosamine are unique among the nitrosamines in their capacity to induce bladder tumours in the rat (Druckrey et al, 1962(Druckrey et al, , 1964. This paper describes the carcinogenic action of DBN administered at two dose levels to C57BL/6 mice.…”

mentioning

confidence: 99%

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Induction of Bladder Tumours in Mice with Dibutylnitrosamine

Bertram¹,

Craig²

1970

Br J Cancer

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SUMMARY.-Dibutylnitrosamine has been administered continuously in the drinking water to two groups of C57BL/6 mice. The first group (50 males, 50 females) received 30 mg./kg./day and the second (50 males, 50 females) 7*6 mg./ kg./day. Of mice reaching autopsy squamous cell carcinoma of the bladder was found in 44/90 at the high dose and 19/89 at the low dose. Bladder tumours were found predominantly in males, the ratio of tumours in males and females being 4.4: 1 and 8-5: 1 at the high and low dose levels, respectively. Carcinomas and papillomas of the oesophagus were found in all but 2 of the females and all but 6 of the males. In addition 5 carcinomas of the fore-stomach in the low dose group and a total in both groups of 13 tumours of the soft palate and tongue were found. The mean cumulative doses and respective induction times for the high and low dose groups were 7*4 and 2-0 g./kg., and 240 and 260 days.N-NITROSO compounds were first shown to be carcinogenic by Magee and Barnes (1956) and have since been the subject of extensive research to determine both their mode of action and their structure-activity relationship. The review by Magee and Barnes (1967) gives a comprehensive coverage of this topic. The dialkyl nitrosamines predominantly produce tumours of the liver, lung, oesophagus, kidney, stomach, nasal sinus and bronchus. Dibutylnitrosamine (DBN) and its hydroxylated derivative butyl-4-hydroxybutylnitrosamine are unique among the nitrosamines in their capacity to induce bladder tumours in the rat (Druckrey et al., 1962(Druckrey et al., , 1964. This paper describes the carcinogenic action of DBN administered at two dose levels to C57BL/6 mice. MATERIALS AND METHODSInbred C57BL/6 mice with a low spontaneous tumour incidence (Green, 1968) were housed in groups of 10 and allowed unlimited access to food (Thomson Diet, Ley et al., 1969) and drinking water containing the carcinogen. Treatment was commenced when 10-12 weeks old. The purity of the DBN used (obtained from Eastman-Kodak) was checked by thin-layer and gas liquid chromatography. Drinking water solutions were changed twice weekly and the volume drunk recorded. The total carcinogenic dose for each mouse was calculated on the assumption that individual mice within a cage consumed similar amounts of water (Clapp and Craig, 1967

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Section: Discussioncontrasting

confidence: 61%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

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Induction of Bladder Tumours in Mice with Dibutylnitrosamine

Bertram¹,

Craig²

1970

Br J Cancer

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“…genic activity in rats by Druckrey et al (1967), N-nitroso-dibutylamine was found to be the only symmetrical dialkylnitrosamine which induced cancer of the urinary bladder. Similarly, the related N-nitrosobutanol-(4)-butylamine (I) was reported to be an even more potent and specific bladder carcinogen, since cancer of this organ was diagnosed in all 25 animals which had received daily doses of the compound as low as 20 mg/kg in drinking water (Druckrey et al, 1964).…”

mentioning

confidence: 97%

Induction of bladder cancer by N-nitroso-dibutylamine and N-nitrososo-butanol-(4)-butylamine

Kolar¹

1972

Br J Cancer

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Hepatocarcinogenic activity of N-butyl-N-(4-hydroxybutyl)nitrosamine in rats is not modified by sodium l-ascorbate

Hagiwara¹,

Mizutani

Yoshino

et al. 1999

Teratog. Carcinog. Mutagen.

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Male F344 and Wistar Shionogi (WS) rats were treated with 0.05% N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine (BBN) for 20 weeks and then killed at week 36 (experiment 1). Although reduction of body weight increase was found, no effects on liver weights were noted. Formalin‐fixed and paraffin‐embedded liver tissues from rats killed terminally were cut and stained for glutathione S‐transferase placental form (GST‐P) immunohistochemically. Marked elevation of quantitative values of small GST‐P positive (GST‐P+) foci were apparent in both strains of rat administered BBN. In experiment 2, both sexes of F344 rats were given 0.05% BBN in the drinking water for 4 weeks and then fed diet containing 0 or 5.0% sodium L‐ascorbate (SA) for 32 weeks. No body and liver weight changes were evident in any group. Quantitative values for small GST‐P+ foci were increased in both sexes of rats exposed to BBN but were not modified by additional SA treatment. Thus, it was confirmed that the selective bladder carcinogen BBN also acts as a liver carcinogen. These results, from the quantitative analysis of small GST‐P+ foci as end point marker lesions, indicate that the liver tumor modifying potential of test chemicals can be evaluated in rats by using an initiation/promotion protocol for urinary bladder carcinogenesis. Teratogenesis Carcinog. Mutagen. 19:33–42, 1999. © 1999 Wiley‐Liss, Inc.

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Selektive Erzeugung von Blasenkrebs an Ratten durch Dibutyl- und N-Butyl-N-butanol(4)-nitrosamin

Cited by 142 publications

References 13 publications

Induction of Bladder Tumours in Mice with Dibutylnitrosamine

Induction of Bladder Tumours in Mice with Dibutylnitrosamine

Induction of bladder cancer by N-nitroso-dibutylamine and N-nitrososo-butanol-(4)-butylamine

Hepatocarcinogenic activity of N-butyl-N-(4-hydroxybutyl)nitrosamine in rats is not modified by sodium l-ascorbate

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