3-amino-1-methyl-5h-pyrido(4-3-b)indole and Neoplasms

Topics: Animals; Breast Neoplasms; Carbolines; Carcinogens, Environmental; Cattle; Colonic Neoplasms; Cooking; Food; Harmine; Head and Neck Neoplasms; Humans; Imidazoles; Male; Meat; Mutagens; Neoplasms; Nitrates; Nitrites; Nitrosamines; Prostatic Neoplasms

In order to examine the carcinogenicity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole acetate (Trp-P-2), 30 male and 30 female F344 rats were maintained on diet containing 0, 30, or 100 ppm Trp-P-2 for 112 weeks. The overall mean chemical intakes in the 100 ppm and 30 ppm groups were 3.84 and 1.14 mg/kg/day in males, and 4.57 and 1.34 mg/kg/day in females, respectively. Females of the 100 ppm group showed increased mortality in the late period of the study. In the 100 ppm group, significant increases in the incidences of neoplastic lesions were found in the liver, urinary bladder and mammary gland in males, and in the mammary gland, hematopoietic system and clitoral gland in females. Histologically, tumors induced by Trp-P-2 were hepatocellular adenomas, transitional cell tumors (papillomas and carcinomas) of the urinary bladder, fibroadenomas/fibromas of the mammary gland, malignant lymphomas and clitoral gland tumors (adenomas and adenocarcinomas). These results indicate multi-target carcinogenicity of Trp-P-2 in F344 rats and provide evidence that the urinary bladder is also a target for heterocyclic amine action.

Topics: Animals; Carbolines; Carcinogens; Diet; Female; Male; Neoplasms; Rats; Rats, Inbred F344; Urinary Bladder Neoplasms

Sensitivities to sister chromatid exchange (SCE) induction by chemicals of peripheral lymphocytes from 26 cancer patients were estimated under conditions identical to those for healthy humans which had been reported (Cancer Res., 43: 439-442, 1983). The sensitive individual was defined as one whose cells give a mean induced SCE frequency more than 2 standard deviation units above the population mean of induced SCEs in cells from the healthy humans. When cells were treated with 3-amino-1-methyl-5H-pyrido[4, 3-b]indole in the presence of rat liver S9 mix, 8 in 10 stomach cancer patients, 4 in 4 colon cancer patients, 3 in 9 lung cancer patients, 0 in 3 patients bearing other cancers, and 0 in 9 non-cancerous individuals were sensitive. The corresponding frequency of individuals in the healthy population, reported previously, was 1 in 33 persons. Thus, the frequency of sensitive individuals in the combined group of stomach and colon cancer patients was very significantly higher than were frequencies in control groups. Three in 10 patients with stomach cancer and 4 in 16 patients with other cancers were sensitive to induction of SCE by methyl methanesulfonate. Six in these 7 methyl methanesulfonate-sensitive patients were also 3-amino-1-methyl-5H-pyrido[4,3-b]indole sensitive. The frequency of methyl methanesulfonate-sensitive individuals in the healthy populations was 2 in 50. There was no patient who was sensitive to SCE induction by 4-nitroquinoline 1-oxide. The frequency was not significantly different from the healthy population, in which 3 in 50 persons were sensitive. These results suggest that a particular cancer correlates with the sensitivity of peripheral lymphocytes to SCE induction by particular chemicals.

Topics: 4-Nitroquinoline-1-oxide; Aged; Carbolines; Colonic Neoplasms; Female; Humans; Lung Neoplasms; Lymphocytes; Male; Methyl Methanesulfonate; Middle Aged; Neoplasms; Sister Chromatid Exchange; Stomach Neoplasms