Carcinogenicity of N-Nitrosomethyl(2-oxobutyl)amine and N-Nitrosomethyl-(3-oxobutyl)amine in Syrian Hamsters with Special Reference to the Pancreas

Parviz M. Pour, Donald Nagel, Terence A Lawson

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Studies with oxidized derivatives of N-nitrosodi-n-propylamine suggested a structure-activity relationship between pancreatic cancer induction in Syrian hamsters and position and degree of nitrosamine oxidation. To elucidate the importance of the position of the oxidized substituent relative to the N-nitroso group in pancreatic carcinogenesis, we compared the toxicity and carcinogenicity of two substituted methylbutylnitrosamines. N-Nitrosomethyl(2-oxobutyl)amine (M-2-OB) and N-nitrosomethyl(3-ox-obutyl)amine (M-3-OB) were given in equitoxic doses to male and female Syrian hamsters. The 50% lethal doses for M-2-OB and M-3-OB in males and females, respectively, were 92 and 160 and 705 and 810 mg/kg body weight. M-2-OB, although given in significantly smaller doses (minimum dose, 2.3 mg/kg body weight) than was M-3-OB (minimum dose, 17.6 mg/kg body weight), induced a much broader spectrum of neoplasms (in 17 tissues), whereas M-3-OB induced tumors in only 5 tissues and had no carcinogenic effect in the pancreas. M-2-OB, however, produced pancreatic ductular-ductal adenocarcinomas in over 90% of the males and 67% of the females, even at the lowest doses (2.3 and 4.0 mg/kg, respectively). Although both compounds caused a similar incidence of morphologically equivalent neoplasms (mostly adenocarcinomas) in the nasal and paranasal cavities, the remaining distribution of affected tissues differed significantly. M-2-OB predominantly affected the lip (epitheliomas, squamous cell carcinomas), liver (cholangiomas and cholangiocarcinomas), and flank organ (epitheliomas, squamous cell carcinomas). The principal target organs for M-3-OB were the cheek pouch (papillomas, squamous cell carcinomas) and trachea (polyps). In contrast to M-2-OB, M-3-OB did not induce renal and urethral tumors. These findings indicate the importance of the 2-oxo group as a prerequisite for the carcinogenicity of methylalkylnitrosamines in the hamster pancreas; however, a methyl group in one aliphatic chain, α to the N-nitroso function, appears to cause the molecule to lose its selectivity for the pancreas.

Original languageEnglish (US)
Pages (from-to)4885-4890
Number of pages6
JournalCancer Research
Volume43
Issue number10
StatePublished - Oct 1 1983

Fingerprint

Mesocricetus
Pancreas
Squamous Cell Carcinoma
Body Weight
Neoplasms
Bile Duct Adenoma
Adenocarcinoma
Propylamines
Carcinoma
Nitrosamines
Cholangiocarcinoma
Cheek
Nasal Cavity
Lethal Dose 50
Papilloma
Tissue Distribution
Structure-Activity Relationship
Lip
Polyps
N-nitrosomethyl(2-oxobutyl)amine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Carcinogenicity of N-Nitrosomethyl(2-oxobutyl)amine and N-Nitrosomethyl-(3-oxobutyl)amine in Syrian Hamsters with Special Reference to the Pancreas. / Pour, Parviz M.; Nagel, Donald; Lawson, Terence A.

In: Cancer Research, Vol. 43, No. 10, 01.10.1983, p. 4885-4890.

Research output: Contribution to journalArticle

@article{51145bebb02040aa91531d5fd2652065,
title = "Carcinogenicity of N-Nitrosomethyl(2-oxobutyl)amine and N-Nitrosomethyl-(3-oxobutyl)amine in Syrian Hamsters with Special Reference to the Pancreas",
abstract = "Studies with oxidized derivatives of N-nitrosodi-n-propylamine suggested a structure-activity relationship between pancreatic cancer induction in Syrian hamsters and position and degree of nitrosamine oxidation. To elucidate the importance of the position of the oxidized substituent relative to the N-nitroso group in pancreatic carcinogenesis, we compared the toxicity and carcinogenicity of two substituted methylbutylnitrosamines. N-Nitrosomethyl(2-oxobutyl)amine (M-2-OB) and N-nitrosomethyl(3-ox-obutyl)amine (M-3-OB) were given in equitoxic doses to male and female Syrian hamsters. The 50{\%} lethal doses for M-2-OB and M-3-OB in males and females, respectively, were 92 and 160 and 705 and 810 mg/kg body weight. M-2-OB, although given in significantly smaller doses (minimum dose, 2.3 mg/kg body weight) than was M-3-OB (minimum dose, 17.6 mg/kg body weight), induced a much broader spectrum of neoplasms (in 17 tissues), whereas M-3-OB induced tumors in only 5 tissues and had no carcinogenic effect in the pancreas. M-2-OB, however, produced pancreatic ductular-ductal adenocarcinomas in over 90{\%} of the males and 67{\%} of the females, even at the lowest doses (2.3 and 4.0 mg/kg, respectively). Although both compounds caused a similar incidence of morphologically equivalent neoplasms (mostly adenocarcinomas) in the nasal and paranasal cavities, the remaining distribution of affected tissues differed significantly. M-2-OB predominantly affected the lip (epitheliomas, squamous cell carcinomas), liver (cholangiomas and cholangiocarcinomas), and flank organ (epitheliomas, squamous cell carcinomas). The principal target organs for M-3-OB were the cheek pouch (papillomas, squamous cell carcinomas) and trachea (polyps). In contrast to M-2-OB, M-3-OB did not induce renal and urethral tumors. These findings indicate the importance of the 2-oxo group as a prerequisite for the carcinogenicity of methylalkylnitrosamines in the hamster pancreas; however, a methyl group in one aliphatic chain, α to the N-nitroso function, appears to cause the molecule to lose its selectivity for the pancreas.",
author = "Pour, {Parviz M.} and Donald Nagel and Lawson, {Terence A}",
year = "1983",
month = "10",
day = "1",
language = "English (US)",
volume = "43",
pages = "4885--4890",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "10",

}

TY - JOUR

T1 - Carcinogenicity of N-Nitrosomethyl(2-oxobutyl)amine and N-Nitrosomethyl-(3-oxobutyl)amine in Syrian Hamsters with Special Reference to the Pancreas

AU - Pour, Parviz M.

AU - Nagel, Donald

AU - Lawson, Terence A

PY - 1983/10/1

Y1 - 1983/10/1

N2 - Studies with oxidized derivatives of N-nitrosodi-n-propylamine suggested a structure-activity relationship between pancreatic cancer induction in Syrian hamsters and position and degree of nitrosamine oxidation. To elucidate the importance of the position of the oxidized substituent relative to the N-nitroso group in pancreatic carcinogenesis, we compared the toxicity and carcinogenicity of two substituted methylbutylnitrosamines. N-Nitrosomethyl(2-oxobutyl)amine (M-2-OB) and N-nitrosomethyl(3-ox-obutyl)amine (M-3-OB) were given in equitoxic doses to male and female Syrian hamsters. The 50% lethal doses for M-2-OB and M-3-OB in males and females, respectively, were 92 and 160 and 705 and 810 mg/kg body weight. M-2-OB, although given in significantly smaller doses (minimum dose, 2.3 mg/kg body weight) than was M-3-OB (minimum dose, 17.6 mg/kg body weight), induced a much broader spectrum of neoplasms (in 17 tissues), whereas M-3-OB induced tumors in only 5 tissues and had no carcinogenic effect in the pancreas. M-2-OB, however, produced pancreatic ductular-ductal adenocarcinomas in over 90% of the males and 67% of the females, even at the lowest doses (2.3 and 4.0 mg/kg, respectively). Although both compounds caused a similar incidence of morphologically equivalent neoplasms (mostly adenocarcinomas) in the nasal and paranasal cavities, the remaining distribution of affected tissues differed significantly. M-2-OB predominantly affected the lip (epitheliomas, squamous cell carcinomas), liver (cholangiomas and cholangiocarcinomas), and flank organ (epitheliomas, squamous cell carcinomas). The principal target organs for M-3-OB were the cheek pouch (papillomas, squamous cell carcinomas) and trachea (polyps). In contrast to M-2-OB, M-3-OB did not induce renal and urethral tumors. These findings indicate the importance of the 2-oxo group as a prerequisite for the carcinogenicity of methylalkylnitrosamines in the hamster pancreas; however, a methyl group in one aliphatic chain, α to the N-nitroso function, appears to cause the molecule to lose its selectivity for the pancreas.

AB - Studies with oxidized derivatives of N-nitrosodi-n-propylamine suggested a structure-activity relationship between pancreatic cancer induction in Syrian hamsters and position and degree of nitrosamine oxidation. To elucidate the importance of the position of the oxidized substituent relative to the N-nitroso group in pancreatic carcinogenesis, we compared the toxicity and carcinogenicity of two substituted methylbutylnitrosamines. N-Nitrosomethyl(2-oxobutyl)amine (M-2-OB) and N-nitrosomethyl(3-ox-obutyl)amine (M-3-OB) were given in equitoxic doses to male and female Syrian hamsters. The 50% lethal doses for M-2-OB and M-3-OB in males and females, respectively, were 92 and 160 and 705 and 810 mg/kg body weight. M-2-OB, although given in significantly smaller doses (minimum dose, 2.3 mg/kg body weight) than was M-3-OB (minimum dose, 17.6 mg/kg body weight), induced a much broader spectrum of neoplasms (in 17 tissues), whereas M-3-OB induced tumors in only 5 tissues and had no carcinogenic effect in the pancreas. M-2-OB, however, produced pancreatic ductular-ductal adenocarcinomas in over 90% of the males and 67% of the females, even at the lowest doses (2.3 and 4.0 mg/kg, respectively). Although both compounds caused a similar incidence of morphologically equivalent neoplasms (mostly adenocarcinomas) in the nasal and paranasal cavities, the remaining distribution of affected tissues differed significantly. M-2-OB predominantly affected the lip (epitheliomas, squamous cell carcinomas), liver (cholangiomas and cholangiocarcinomas), and flank organ (epitheliomas, squamous cell carcinomas). The principal target organs for M-3-OB were the cheek pouch (papillomas, squamous cell carcinomas) and trachea (polyps). In contrast to M-2-OB, M-3-OB did not induce renal and urethral tumors. These findings indicate the importance of the 2-oxo group as a prerequisite for the carcinogenicity of methylalkylnitrosamines in the hamster pancreas; however, a methyl group in one aliphatic chain, α to the N-nitroso function, appears to cause the molecule to lose its selectivity for the pancreas.

UR - http://www.scopus.com/inward/record.url?scp=0020579615&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020579615&partnerID=8YFLogxK

M3 - Article

VL - 43

SP - 4885

EP - 4890

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 10

ER -