Mechanisms of Differential Strain Sensitivity in Gastric Carcinogenesis

• Published in: Japanese Journal of Cancer Research Vol. 79; no. 12; pp. 1304 - 1310
• Main Authors: Weisburger, John H., Jones, R. Conrad, Barnes, William S., Pegg, Anthony E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-12-1988; Japanese Cancer Association
• Subjects: Animals; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; DNA Repair; DNA synthesis and repair; Gastric cancer; Gastric Mucosa - analysis; Glutathione; Glutathione - analysis; Male; Medical sciences; Methylnitronitrosoguanidine; Methyltransferases - analysis; N‐Methyl‐N′‐nitro‐N‐nitrosoguanidine; O-Methylguanine-DNA Methyltransferase; O6‐Alkylguanine alkyltransferase; Rats; Rats, Inbred Strains; Species Specificity; Stomach Neoplasms - chemically induced; Sulfhydryl Compounds - analysis; Tumors; Stomach; Vertebrata; Mammalia; Duodenum; Rat; Animal; Rodentia; Tumor; Strain specificity; Mechanism of action; Carcinogenesis
• ISSN: 0910-5050; 1349-7006; 1876-4673
• DOI: 10.1111/j.1349-7006.1988.tb01560.x

The genetically‐controlled, distinct sensitivity of different rat strains to N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG)‐induced cancer of the glandular stomach and duodenum was investigated. MNNG is activated through thiols, and the thiol content of the glandular stomach, duodenum, and liver of the BN rat tended to be slightly, but not significantly higher than that of the Wistar, Sprague‐Dawley, Lewis, and Buffalo rats. The levels of the DNA repair system, O6‐alkylguanine transferase (AGT), in sensitive Wistar strain rats had values similar to those in resistant Buffalo strain rats. Administration of 80 mg/liter of MNNG in the drinking water for six weeks up to the time of tissue collection yielded the same AGT levels. Of all the parameters examined to account for genetically‐mediated sensitivity to gastrointestinal cancer induction, namely, N‐denitrosation, thiol activation, AGT‐related DNA repair, and cell duplication rates, the latter yielded the best association, although these factors acting together may be involved.