The Carcinogenic Action of Aflatoxin after its Subcutaneous Injection in the Rat

Dickens, F.; Jones, Helen

doi:10.1038/bjc.1963.88

Cited by 76 publications

(28 citation statements)

References 7 publications

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“…The administration of patulin subcutaneously twice a week for 15 months showed the development of malignant tumor cells in the area of administration which proved the carcinogenic effect of this mycotoxin. It can by hypothesized in humans as well (64,(194)(195)(196) although the carcinogenic effect of patulin was not confirmed by Osswald at al (197), patulin was confirmed to be toxic to the mice born to patulin treated mothers and deaths occurred in both males and females.…”

Section: Mycotoxins and Their Carcinogenicitymentioning

confidence: 99%

Effects of different mycotoxins on humans, cell genome and their involvement in cancer

et al. 2017

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Abstract. The chemical nature of most of the mycotoxins makes them highly liposoluble compounds that can be absorbed from the site of exposure such as from the gastrointestinal and respiratory tract to the blood stream where it can be dissimilated throughout the body and reach different organs such as the liver and kidneys. Mycotoxins have a strong tendency and ability to penetrate the human and animal cells and reach the cellular genome where it causes a major mutagenic change in the nucleotide sequence which leads to strong and permanent defects in the genome. This defect will eventually be transcribed, translated and lead to the development of cancer. In this review, the chemical and physical nature of mycotoxins, the action of mycotoxins on the cellular genome and its effect on humans, mycotoxins and their carcinogenicity and mycotoxins research gaps are discussed, and new research areas are suggested. The research review posed various questions. What are the different mycotoxins that can cause cancer, what is the role of mycotoxins in causing cancer and what types of cancers can be caused by mycotoxins? These questions have been selected due to the significant increase in the mycotoxin contamination and the cancer incidence rate in the contemporary world. By revealing and understanding the role of mycotoxins in developing cancer, measures to reduce the risks and incidents of cancer could be taken.

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Section: Mycotoxins and Their Carcinogenicitymentioning

confidence: 99%

Effects of different mycotoxins on humans, cell genome and their involvement in cancer

et al. 2017

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“…The four naturally occurring AFs, aflatoxins B1 (AFB1), B2 (AFB2), G1 (AFG1), and G2 (AFG2), when administered as mixtures, were a potent class of animal hepatocarcinogens (2-6). They have been also associated with neoplastic formations in tissues and organs other than the liver (3,(6)(7)(8)(9).Tests with rats (10) and rainbow trout (11) have revealed that AFB1 is a potent hepatocarcinogen; AFG1 is also considerably carcinogenic, but AFB2 and AFG2 possess much lower activity. Recent studies on the metabolism of AFB1 have resulted in the isolation and identification of numerous metabolites, all of minor structural variations but significantly different biological activity relative to the parent compound (12).…”

mentioning

confidence: 99%

Mutagenicity of aflatoxins related to their metabolism and carcinogenic potential.

Wong¹,

Hsieh²

1976

Proc. Natl. Acad. Sci. U.S.A.

222

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Aflatoxins and their animal biotransformation products were screened for carcinogenic potential using the Ames' in vitro microbial detection system for carcinogens as bacterial mutagens [B. N. Ames et aL (1973) Proc (1). The four naturally occurring AFs, aflatoxins B1 (AFB1), B2 (AFB2), G1 (AFG1), and G2 (AFG2), when administered as mixtures, were a potent class of animal hepatocarcinogens (2-6). They have been also associated with neoplastic formations in tissues and organs other than the liver (3,(6)(7)(8)(9).Tests with rats (10) and rainbow trout (11) have revealed that AFB1 is a potent hepatocarcinogen; AFG1 is also considerably carcinogenic, but AFB2 and AFG2 possess much lower activity. Recent studies on the metabolism of AFB1 have resulted in the isolation and identification of numerous metabolites, all of minor structural variations but significantly different biological activity relative to the parent compound (12).Among these metabolites, aflatoxins Q, (AFQ1), M1 (AFM1), Bk (AFBa), and P1 (AFP1), aflatoxicol (AFL), and aflatoxicol H1 (AFLH1) (Table 1) are the biotransformation products of AFB1 when the latter is incubated with liver preparations and a NADPH-generating system (13-17). Since evidence has indicated that AFB1 requires metabolic activation for its toxic, mutagenic, and/or carcinogenic activity (18)(19)(20)(21)(22), the toxicity of each metabolite has been of great interest in the search for the active molecular species. Attempts have been made to correlate the relative activity of the different metabolic pathways and the variations in the species susceptibility to aflatoxicosis (16,23 (24,25). The analysis of the known major AF metabolites in our study permits an observation of the structureactivity relationships as related to the carcinogenic potential of the AFs. MATERIALS AND METHODSChemicals are obtained as follows: AFBI, AFG1, AFB2, and AFG2 were purchased from Makor Chemicals, Ltd., Jerusalem, Israel. AFM1, AFQ1, and AFH1 were prepared by biotransformation of AFB1 using monkey liver homogenates (14, 17). AFL was prepared by a similar biotransformation method to be published elsewhere. AFB2k and AFGk were chemically synthesized from AFB1 with dilute acid (27). AFP1 was a chemically synthesized product kindly provided by G. N. Wogan, Massachusetts Institute of Technology, Cambridge, Mass. The purity and identity of all AFs was checked by fluorodensitometric analysis of thin-layer chromatography plates and mass spectrometry. In addition, AFQ1, AFM1, AFH1, and AFB2k were checked by high-pressure liquid chromatography (28). All biochemicals, NADP+, glucose 6-phosphate, histidine, and biotin, were purchased from Sigma Chemicals, St. Louis, Mo.The bacterial tester strain, Salmonella typhimurium strain TA 98 (21), was the generous gift of B. N. Ames, University of California, Berkeley. The bacteria were stored and grown as outlined by McCann et al. (21). The hepatic S-9 enzyme preparation was prepared from Charles River male white rats (200-250 g) and utilized according to procedur...

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“…exposure to AFB,, so, with this mode of administration, it is possible that unmetabolized AFB, could reach bone marrow cells. AFB, is also carcinogenic in extrahepatic tissues: it induces carcinomas at low incidence in the glandular stomach (10) and fibrosarcomas are inducible at the site of injection when AFB, is given several times in doses of 50 and 500 /tg subcutaneously (12). However, the absence of mutagenic activity after oral application most likely is due to the efficient activation of AFB, in the liver, where the chemical is converted to the ultimate carcinogen, the reactive 2,3-oxide (20), in a single, cytochrome P-450-dependent step and interacts mainly at sites where these enzymes are accumulated.…”

Section: Discussionmentioning

confidence: 99%

Hepatocarcinogens induce gene mutations in rats in fibroblast-like cells from a subcutaneous granulation tissue

Maier

Schawalder

1988

Carcinogenesis

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'To whom reprint requests should be sent Gene-mutations at the 6-thioguanine locus, in Hbroblast likecells rapidly proliferating on the inside of rat subcutaneous air pouches were analysed (Granuloma Pouch Assay). Target cells were exposed directly by injection into the air pouch, or systemicaliy by oral or intraperitoneal administration to three hepatocarcinogens aflatoxin B,, 2-acetyIaminofluorene (2-AAF) and vinylchloride. In addition ethylnitrosourea (ENU) was used as a positive control, and 2-aminofluorene to characterize the pharmacokinetic behaviour of 2-AAF. When administered directly, all chemicals except 2-AAF induced a dose-dependent increase in gene-mutation frequencies. However, 2-AAF was mutagenic after oral administration. The highest inducible mutation frequencies found with the hepatocarcinogens were 8 to 10 times the spontaneous mutation frequency, but only ~ 10% of that found with the control mutagen ENU. The known enzymic activation capacity of the granulation tissue, and the mutagenic activity of other chemicals in this system already reported, suggest that after direct exposure, the prostaglandin H synthetase pathway or lipoxygenases are involved in the activation of the hepatotoxins to gene mutation inducing species in vivo. 2-AAF seems to be converted via stable intermediates to the ultimate mutagenic species in the extrahepatic target tissues.

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The Carcinogenic Action of Aflatoxin after its Subcutaneous Injection in the Rat

Abstract: Images Figs. 1-3

Cited by 76 publications

References 7 publications

Effects of different mycotoxins on humans, cell genome and their involvement in cancer

Effects of different mycotoxins on humans, cell genome and their involvement in cancer

Mutagenicity of aflatoxins related to their metabolism and carcinogenic potential.

Hepatocarcinogens induce gene mutations in rats in fibroblast-like cells from a subcutaneous granulation tissue

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