Potential genotoxic,mutagenic and antimutagenic effects of coffee: A review

Coffee and caffeine are mutagenic to bacteria and fungi, and in high concentrations they are also mutagenic to mammalian cells in culture. However, the mutagenic effects of coffee disappear when bacteria or mammalian cells are cultured in the presence of liver extracts which contain detoxifying enzymes. In vivo, coffee and caffeine are devoid of mutagenic effects. Coffee and caffeine are able to interact with many other mutagens and their effects are synergistic with X-rays, ultraviolet light and some chemical agents. Caffeine seems to potentiate rather than to induce chromosomal aberrations and also to transform sublethal damage of mutagenic agents into lethal damage. Conversely, coffee and caffeine are also able to inhibit the mutagenic effects of numerous chemicals. These antimutagenic effects depend on the time of administration of coffee as compared to the acting time of the mutagenic agent. In that case, caffeine seems to be able to restore the normal cycle of mitosis and phosphorylation in irradiated cells. Finally, the potential genotoxic and mutagenic effects of the most important constituents of coffee are reviewed. Mutagenicity of caffeine is mainly attributed to chemically reactive components such as aliphatic dicarbonyls. The latter compounds, formed during the roasting process, are mutagenic to bacteria but less to mammalian cells. Hydrogen peroxide is not very active but seems to considerably enhance mutagenic properties of methylglyoxal. Phenolic compounds are not mutagenic but rather anticarcinogenic. Benzopyrene and mutagens formed during pyrolysis are not mutagenic whereas roasting of coffee beans at high temperature generates mutagenic heterocyclic amines. In conclusion, the mutagenic potential of coffee and caffeine has been demonstrated in lower organisms, but usually at doses several orders of magnitude greater than the estimated lethal dose for caffeine in humans. Therefore, the chances of coffee and caffeine consumption in moderate to normal amounts to induce mutagenic effects in humans are almost nonexistent.     

3-Methoxy-4-aminoazobenzene, a unique carcinogenic aromatic amine as a substrate for cytochrome-P-450-mediated mutagenesis

Rat liver microsomal enzyme(s) that catalyze mutagenic activation of a carcinogenic aminoazo dye, 3-methoxy-4-aminoazobenzene (3-MeO-AAB), was studied by virtue of the Salmonella typhimurium TA98 assay using o-aminoazotoluene (OAT) as the control. Male Wistar rats were pretreated with phenobarbital (PB), 3-methylcholanthrene (MC) or polychlorinated biphenyl (PCB), and the liver microsomal activities for mutagenic activation of 3-MeO-AAB and OAT were examined. In agreement with the reported results on several carcinogenic aromatic amines, MC pretreatment resulted in greater activation of microsomal activity in the OAT mutagenesis (about a 4-fold increase as compared to the untreated control) than did PB (1.5-fold increase). By contrast, the mutagenic activation of 3-MeO-AAB is found to be more efficiently catalyzed by those enzyme(s) that are induced by PB pretreatment (4-fold increase) than by those that are induced by MC (1.8-fold increase). The induced enzymes that principally mediate the mutagenic activation of these azo dyes are indicated to be cytochrome P-450s, because the mutagenic activation was strongly inhibited by addition of cytochrome P-450 inhibitors such as 2-diethylaminoethyl-2,2-diphenylvalerate (SKF 525A) and 7,8-benzoflavone. These data suggest that 3-MeO-AAB is a unique carcinogenic aromatic amine as a substrate for mutagenic activation via catalysis of those cytochrome P-450s that are induced by PB pretreatment.     

Mutagenicities of quinoline and its derivatives.

Quinoline, recently reported to be carcinogenic in rats [12], was mutagenic to Salmonella typhimurium tester strains TA100 and TA98 in the presence of the metabolic activation system S-9 mix. 2-Chloroquinoline, a non-carcinogen [12], was non-mutagenic with or without S-9 mix. 8-Hydroxyquinoline, which is t known to be carcinogenic, was mutagenic with S-9 mix to both bacterial strains. The mutagenicities of 17 other quinoline derivatives that are not known to be carcinogenic were tested, and 12 of these compounds were mutagenic.     

Relationship between the induction of micronuclei in marrow cells by chromium salts and their carcinogenic properties

The micronucleus test has been used to study the mutagenic activity of chromium derivatives and to examine the relationship between their carcinogenic properties and their ability to induce chromosomal damage. It has been found that potassium dichromate is a potent mutagen increasing, for instance, the rate of micro-nucleated erythrocytes while calcium chromate and chromic nitrate are ineffective. From our observations and the data on carcinogenicity, it can be concluded that the micronucleus test cannot be used to predict the carcinogenic properties of chromium derivatives.     

Metabolic studies and the evaluation of genetic risk from the viewpoint of industrial toxicology

In recent years some important industrial chemicals, e.g. solvents, and monomers used in the production of plastics, have been found to be more dangerous than had been suspected. Some of them are mutagens and carcinogens. The active substance may be the compound itself, but more frequently it is a reactive intermediate, an alkylating agent, formed from the parent compound by oxidation under the influence of liver-microsome mixed-function oxidases. Trichloroethylene, vinyl chloride, 1,1-dichloroethylene and 2-chloro-1,3-butadiene can be mentioned as examples, where mutagenic or carcinogenic activity has been demonstrated; similar activity of some others is to be suspected. Metabolic studies may explain unexpected effects or they may allow one to predict such effects. Tests on microorganisms with a metabolic activation in vitro seem to be extremely valuable for fast and efficient screening of man-made chemicals to be introduced into the environment, because such tests combine the use of liver microsomes and bacteria for the detection and classification of the effect. Mutagenicity tests in mammals do not lose their usefulness, since they take into account the distribution of the compound in the body, its transport to the target organ, species-specific differences etc. As exposures of workers to chemicals mentioned above have been quantitatively measured regularly, epidemiological studies should be performed with regard to mutagenic and carcinogenic effects in relation to the degree of exposure. Here is a chance for better understanding of how to extrapolate experimental results to human populations and how to establish safe levels of chemicals in the environment if at all possible and acceptable.     

Vanadium and tungsten derivatives as antidiabetic agents: a review of their toxic effects

Tungstate is an oxyanion that has biological similarities to vanadate. In recent years, a number of studies have shown the antidiabetic effects of oral tungstate in animal models of diabetes. However, because of the tissue accumulation and potential toxicity derived from chronic administration of vanadium and tungsten compounds, the pharmacological use of vanadate or tungstate in the treatment of diabetes is not necessarily exempt from concern. In the context of a potential use in the treatment of human diabetes mellitus, the most relevant toxic effects of vanadium derivatives are reviewed and compared with those reported for tungsten. Hematological and biochemical alterations, loss of body weight, nephrotoxicity, immunotoxicity, reproductive and developmental toxicity, and behavioral toxicity have been reported to occur following exposure to vanadium compounds. Moreover, vanadium also has a mitogenic activity affecting the distribution of chromosomes during mitosis and inducing aneuploidyrelated end points. In contrast to vanadate, studies about the toxic effects of tungstate are very scant. Early investigations in cats, rabbits, dogs, mice, and rats showed that tungstate was less toxic than vanadate when given intravenously. Although in vitro investigations showed a direct effect of tungstate on the embryo and fetus of mice at concentrations similar to those causing effects in vivo, information on the potential cellular toxicity of tungstate is particularly scarce. Taking into account the recent interest of tungstate as a new potential oral antidiabetic agent, an exhaustive evaluation of its toxicity in mammals is clearly necessary.     

Mutagens and the tumor promoter

We studied the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) and saccharin on the frequency of induced mutations of resistance to 6-mercaptopurine and ouabain in Chinese hamster and mouse cells. UV-rays, bovine adenovirus-3 (BAV-3) and 5-bromdeoxyuridine (BrdU) were used as mutagens. In the case of BAV-3 and BrdU, we investigated, apart from the mutagenic effect, the tumor-inducing activity of these mutagens in mice, BrdU proved to have no carcinogenic effect. The data about the influence of TPA on the mutagenic effect of the three different mutagens indicate that TPA increases the frequency of the gene mutations induced by UV-rays and BAV-3. The results of the study of BrdU and TPA combined action revealed the fact that TPA does not increase the mutagenic effect of BrdU. We demonstrated that saccharin also possesses the promoter activity; it increases the mutagenic effect of BAV-3. The results described above lead to the assumption that TPA influence on the mutagenic effect only takes place when carcinogenic mutagens are used.     

On the mutagenicity of nitroimidazoles

Regarding mutagenicity, metronidazole is one of the best-investigated compounds of the nitroimidazoles. This drug is mutagenic on bacteria, especially if base-pair tester strains are used and bacterial nitroreductases are present. The serum levels attained in man after intake of this drug are sufficient to cause mutations in bacteria. Furthermore, interaction with and binding to DNA occurs under anaerobic conditions and sometimes DNA breaks are observed. However, metronidazole does not show mutagenic activity in mammalian cells in vitro; the micronucleus test is negative and chromosome aberrations are only found under anaerobic conditions. With microbial systems the mutagenicity of 47 nitroimidazoles has been investigated. Only 4 compounds were always negative in the applied test systems. Because with base-pair tester strains mutagenicity was assessed, this class of compounds should be regarded as a base-pair mutagen. In fungi, some compounds (e.g. ZK 26173 and azathioprine) are potent mutagens, whilst with most investigated nitroimidazoles only a weak or no mutagenic activity could be detected. Somewhat similar observations have been made in tests with Drosophila melanogaster, a test for gene mutations in mammalian cells, the micronucleus test, cytogenic tests and the dominant lethal test. The reduction products of metronidazole, misonidazole and 1-methyl-2-nitro-5-vinylimidazole, cause DNA damage if the nitro group is reduced in the presence of DNA. Reduction products are formed by microbes in the gut or by mammalian cells under anaerobic conditions. No teratological effect due to metronidazole or most other nitroimidazoles has been observed. Metronidazole is carcinogenic in mice and rats, and dimetridazole in rats. Up to the present, no carcinogenic effects have been observed in man. Azathioprine is probably carcinogenic for man. It is unlikely that the therapeutic applications of the presently used nitroimidazoles, except for azathioprine, will cause an increase in the tumor incidence in man or will cause other genotoxic effects, although such effects cannot be excluded with certainty.     

Application of the cell growth and DNA-inhibition tests for characterizing sulfate pulp mill waste waters

The evaluation of cytotoxic and genotoxic effects of selected technological samples from sulfate pulp mill waste waters by using the growing activity method for pseudodiploid fibroblasts V79 from lungs of the Chinese hamster and from human heteroploid fibroblasts EUE has been described along with the DNA-inhibition test for studying the synthesis of DNA after it has been influenced by the above-mentioned samples. Both the waste solution produced during the preparation of bleaching agents and the liquor generated after using hypochlorite (1st stage) as a fourth filter (after the production of paper pulp) are cytotoxic waste waters. Black liquor generated during the production of viscose pulp may have mutagenic effects and black liquor obtained from the production of paper pulp is characterized by mutagenic as well as carcinogenic effects.     

Mutagenicity of 43 structurally related heterocyclic compounds and its relationship to their carcinogenicity.

43 heteropolycyclic compounds belonging to a homologous series were investigated for mutagenicity. The results are compared with carcinogenicity data obtained with the same batches of compounds under conditions identical for all of them. Mutagenicity was tested in the Ames test with Salmonella typhimurium strains TA1535, TA1537 and TA100 in the presence and absence of liver 10 000 g supernatant from rats treated with Aroclor 1254. Carcinogenicity was tested by injection of the compounds into subcutaneous tissue of XVIInc/Z mice. 18 test compounds showed carcinogenic activity, some strongly, others only weakly. Of these, 17 were detected as mutagens: one weak carcinogen did not revert the Salmonella strains. No quantitative correlation was observed between the extents of the mutagenic and the carcinogenic effects. Of the 25 substances that did not produce tumours, 13 showed mutagenicity (12 in the presence, 2 in the absence, of the liver homogenate). The mutagenic effects of these compounds were quantitatively similar to those of the compounds that produced tumours. The most sensitive strain of Salmonella typhimurium was TA100. It detected all 30 mutagens. TA98 was mutated by 25 compounds, TA1537 by 16 compounds. No mutagenic effects were seen with TA1535. Possible reasons for the high percentage of apparently "false positives" in the Ames test and the lack of a quantitative correlation between the potency of the mutagenic and carcinogenic effects are discussed. It is suggested that the complexity of the metabolism of these heterocyclic compounds may lead to critical differences in metabolism in mouse subcutaneous tissue in vivo and in liver homogenates from rats treated with Aroclor. Therefore the present study will be extended to life-long oral and intrahepatic carcinogenicity tests leading to a higher proportion of metabolism in the liver.     

Mycotoxins: food contamination, mechanism, carcinogenic potential and preventive measures

Mycotoxins constitute a large number of naturally occurring fungal secondary metabolites with very diversified toxic effects in humans and animals. Among many mycotoxins discovered, aflatoxins, ochratoxin A, sterigmatocystin and several others are identified as carcinogens; several others were found to be mutagenic. Nevertheless, aflatoxin B1 has been found to be one of the most potent carcinogens and contamination of aflatoxins in the food supply is still a major concern. Whereas extensive studies have been made on aflatoxins, little is known about the mode of action of other carcinogenic and mutagenic mycotoxins. Recent progress on research for the carcinogenic and mutagenic mycotoxins is presented in this review with emphasis on their contamination in foods, their carcinogenic potential to humans, and the mode of action as well as possible preventive measures.     

Induction of gene mutations and the lethal action of ultraviolet rays in synchronized Chinese hamster cells

Lethal and mutagenic effects of UV light were studied in two synchronized UV-sensitive Chinese hamster cell clones differing in the degree of sensitivity (CHS1, CHS2). It is shown that the phase of mitosis is most resistant to the lethal effect of UV. The sensitivity of both cell clones increases in the pre-synthetic phase and reaches its maximum during the phase of DNA synthesis. Positive correlation of cell sensitivity to mutagenic and lethal action of UV was observed when studying induced mutability in both cell clones during the phase of DNA synthesis. However, the study of the mutagenic effect of UV on different phases of the synthesis. However, the study of the mutagenic effect of UV on different phases of the cell cycle (M, G1, S) in the less UV-sensitive cell clone has revealed that the maximal mutation yield takes place when cells are irradiated at G1 (CHS1). The discrepancy observed may be due to different probability of the phenotypic detection of pre-mutational lesions, arising at different phases of the cell cycle. It is shown that only one cell generation is necessary for the expression of pre-mutational changes. These data allow to conclude that the increased mutation rate observed at G1 (as compared with S) reveals rather a probability of the expression but not of the occurrence of pre-mutational lesions. It is suggested that the fixation of mutations in the cells studied proceeds during the post-replication repair synthesis.     

Mutagenicity,carcinogenicity, and teratogenicity of acrylonitrile

Acrylonitrile (AN) is an important intermediary for the synthesis of a variety of organic products, such as artificial fibres, household articles and resins. Although acute effects are the primary concern for an exposure to AN, potential genotoxic, carcinogenic and teratogenic risks of AN have to be taken seriously in view of the large number of workers employed in such industries and the world-wide population using products containing and possibly liberating AN. An understanding of the effect of acrylonitrile must be based on a characterization of its metabolism as well as of the resulting products and their genotoxic properties. Tests for mutagenicity in bacteria have in general been positive, those in plants and on unscheduled DNA synthesis doubtful, and those on chromosome aberrations in vivo negative. Wherever positive results had been obtained, metabolic activation of AN appeared to be a prerequisite. The extent to which such mutagenic effects are significant in man depends, however, also on the conditions of exposure. It appears from the limited data that the ultimate mutagenic factor(s), such as 2-cyanoethylene oxide, may have little opportunity to act under conditions where people are exposed because it is formed only in small amounts and is rapidly degraded. The carcinogenic action of AN has been evaluated by various agencies and ranged from `reasonably be anticipated to be a human carcinogen' to `cannot be excluded', the most recent evaluation being `possibly carcinogenic to humans'. Animal data that confirm the carcinogenic potential of AN have certain limitations with respect to the choice of species, type of tumors and length of follow up. Epidemiological studies which sometimes, but not always, yielded positive results, encounter the usual difficulties of confounding factors in chemical industries. Exposure of workers to AN should continue to be carefully monitored, but AN would not have to be considered a cancer risk to the population provided limitations on releases from consumer products and guidelines on AN in water and air are enforced. AN is teratogenic in laboratory animals (rat, hamster) at high doses when foetal/embryonic (and maternal) toxicity already is manifest. Pregnant workers should not be exposed to AN. In view of the small concentrations generally encountered outside plants, women not professionally exposed would appear not to be at risk of teratogenic effects due to AN. Future research should concentrate on the elucidation of the different degradation pathways in man and on epidemiological studies in workers including pregnant women, assessing also, if possible, individual exposure by bio-monitoring.     

Mutagenicity, carcinogenicity, and teratogenicity of acrylonitrile.

Acrylonitrile (AN) is an important intermediary for the synthesis of a variety of organic products, such as artificial fibres, household articles and resins. Although acute effects are the primary concern for an exposure to AN, potential genotoxic, carcinogenic and teratogenic risks of AN have to be taken seriously in view of the large number of workers employed in such industries and the world-wide population using products containing and possibly liberating AN. An understanding of the effect of acrylonitrile must be based on a characterization of its metabolism as well as of the resulting products and their genotoxic properties. Tests for mutagenicity in bacteria have in general been positive, those in plants and on unscheduled DNA synthesis doubtful, and those on chromosome aberrations in vivo negative. Wherever positive results had been obtained, metabolic activation of AN appeared to be a prerequisite. The extent to which such mutagenic effects are significant in man depends, however, also on the conditions of exposure. It appears from the limited data that the ultimate mutagenic factor(s), such as 2-cyanoethylene oxide, may have little opportunity to act under conditions where people are exposed because it is formed only in small amounts and is rapidly degraded. The carcinogenic action of AN has been evaluated by various agencies and ranged from 'reasonably be anticipated to be a human carcinogen' to 'cannot be excluded', the most recent evaluation being 'possibly carcinogenic to humans'. Animal data that confirm the carcinogenic potential of AN have certain limitations with respect to the choice of species, type of tumors and length of follow up. Epidemiological studies which sometimes, but not always, yielded positive results, encounter the usual difficulties of confounding factors in chemical industries. Exposure of workers to AN should continue to be carefully monitored, but AN would not have to be considered a cancer risk to the population provided limitations on releases from consumer products and guidelines on AN in water and air are enforced. AN is teratogenic in laboratory animals (rat, hamster) at high doses when foetal/embryonic (and maternal) toxicity already is manifest. Pregnant workers should not be exposed to AN. In view of the small concentrations generally encountered outside plants, women not professionally exposed would appear not to be at risk of teratogenic effects due to AN. Future research should concentrate on the elucidation of the different degradation pathways in man and on epidemiological studies in workers including pregnant women, assessing also, if possible, individual exposure by bio-monitoring.     

Bacterial systems for carcinogenicity testing

During the past 30 years, bacterial test systems have been extensively refined in their ability to detect not only mutagenic agents but, in many cases, carcinogenic ones as well. Since many carcinogens are known to be activated within the mammalian body, major improvements in bacterial test systems were made when representative parts of mammalian metabolism were included as part of the test protocol. Presently, systems of great simplicity and convenience are available for the efficient detection of gene mutations, lysogenic induction of prophages, and differential DNA repair. These qualities render bacterial systems potentially useful in distinguishing between carcinogens and non-carcinogens, in characterizing induced mutation spectra, and possibly in quantifying mutagenic potency that may be used to predict tumor-initiating potency. Sensitive strains of Salmonella typhimurium. Escherichia coli and Bacillus subtilis with altered DNA-repair capacities have been constructed which accurately identify many carcinogens. Comparative studies have shown that techniques using these strains can be standardized to some extent and that the majority of carcinogens are active in all adequately sensitive genetic systems. Because of this redundancy, it may be sufficient to employ only one standardized set of tester strains and methodology. However, serveral classes of known carcinogens are undetected or underestimated when assayed in standard testing procedures. Some of these chemicals can be efficiently recognized as mutagens upon varying the methodology, the genetic endpoint, or the mammalian activation system. Thus, to modify and adjust the experimental protocol to the particular type of chemical under study and to calibrate the system with appropriate carcinogenic and non-carcinogenic reference compounds is advisable. It is noteworthy that chemical carcinogens which probably act by non-genotoxic mechanisms thus far remain undetected in bacterial tests. Newly developed systems which measure specific types of genetic events, such as transpositions of DNA segments and derepression of genes, presently are being tested for their ability to detect such carcinogens. A final matter of growing concern is the increasing number of environmental chemicals that are found to be mutagenic in bacteria but for which information about carcinogenic activity in vivo is insufficient. The possible use of bacteria for quantifying mutagenic potency and extrapolating this information to tumor-initiating potency can be envisaged in three ways: (i) direct extrapolation from standard in vitro tests, (ii) indirect extrapolation making use of an in vitro/in vivo comparison of induced effects (the parallelogram method) as devised by Sobels [138] on the basis of identical dose (to DNA), and (iii) host-mediated assays to assess mutagenic potency of carcinogens in selected organs of mammals...     

A review of the mutagenicity and rodent carcinogenicity of ambient air

Although ambient air was first shown to be carcinogenic in 1947 and mutagenic in 1975, no overarching review of the subsequent literature has been produced. Recently, Claxton et al. [L.D. Claxton, P.P. Matthews, S.H. Warren, The genotoxicity of ambient outdoor air, a review: Salmonella mutagenicity, Mutat. Res./Rev. Mutat. Res. 567 (2004) 347-399] reviewed the literature on the mutagenicity of urban air in the Salmonella mutagenicity assay. Here, we review the literature on the mutagenicity of urban air in other test systems and review the carcinogenicity of urban air in experimental systems. Urban air was carcinogenic in most of the reports involving rodents. Studies ascribed carcinogenic activity primarily to PAHs, nitroarenes, and other aromatic compounds. Atmospheric conditions, along with the levels and types of pollutants, contributed to the variations in carcinogenic and mutagenic activity of air from different metropolitan areas. The majority of the mutagenesis literature was in the Salmonella assay (50%), with plant systems accounting for most of the rest (31%). The present data give little support to the use of plant systems to compare air mutagenicity among multiple sites or studies. Studies in mice have shown that particulate air pollution causes germ-cell mutations. Air sheds contain similar types and classes of mutagens; however, the levels of these compounds vary considerably among air sheds. Combustion emissions were associated with much of the mutagenicity and carcinogenicity of urban air. Most studies focused on the particulate fraction; thus, additional work is needed on the volatile and semi-volatile fractions, metals, and atmospheric transformation. Smaller particles have greater percentages of extractable organic material and are more mutagenic than larger particles. Although hundreds of genotoxic compounds have been identified in ambient air, only a few (<25) are routinely monitored, emphasizing the value of coupling bioassay with chemistry in the monitoring of air for carcinogenic and mutagenic activities and compounds.     

Impaired immunological surveillance by 7,12-dimethylbenz(a)anthracene augments its skin tumorigenicity in C3H mice

7,12-dimethylbenz(a)anthracene (DMBA) is a polyaromatic hydrocarbon with potent mutagenic, carcinogenic and immunomodulatory activities. It has been postulated that the immunosuppressive effects of DMBA may contribute to the carcinogenicity of this agent. We investigated this issue by examining whether the pre-administration of DMBA at one skin site would augment its carcinogenic activity at a distant skin site. In animals placed on a cutaneous chemical carcinogenesis protocol to the skin of the back, pre-sensitization with DMBA to the abdomen augmented skin tumorigenicity whether the tumor data are considered as cumulative number of tumors, percent of mice with tumors, number of tumors per mouse, or numbers of tumors per tumor bearing mouse as a function of weeks on test. These data demonstrate that pre-treatment with DMBA augments its skin tumorigenicity by impairing immunological surveillance.     

The action of the tumour promoter, TPA, on mutagenesis induced by different agents (UV light, chemical and viral mutagens)

The present paper deals with effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the frequency of induced mutations to 6-mercaptopurine (6MP) and ouabain resistance in Chinese hamster and mouse cells. UV light, bovine adenovirus 3(BAV-3) and 5-bromodeoxyuridine (BrdU) were used as mutagens. TPA was shown to raise the frequency of gene mutations induced by UV light and BAV-3 but it did not enhance the mutagenic effect of BrdU. We also examined the ability of BAV-3 and BrdU to induce tumours in mice. BrdU was shown to have no carcinogenic effect. The results suggest that TPA enhances the mutagenic effect only for carcinogenic mutagens.     

Mutagenic and carcinogenic actions of some polycyclic aromatic hydrocarbons]

The carcinogenic and mutagenic actions of benz(a)pyrene (BP) and its derivatives 6-methyl-, 6-formyl-, 6-chloro-, 6-hydroxy-, 6-acetoxy-, 6-methoxy- and 4(5)-methoxy-BP were studied in mice and bacteria Salmonella typhimurium TA-98 and TA-100, respectively. The potent carcinogenic agents BP, 6-methyl-, 6-formyl-BP proved also mutagenic in bacteria of both strains. Weak carcinogenic compounds (6-chloro-, 6-methoxy-, 4(5)-methoxy-BP) and noncarcinogenic ones (6-acetoxy-, 6-hydroxy-BP) either turned out nonmutagenic or mutagenic in one of two bacterial strains tested. The differences in carcinogenic and mutagenic actions of the substances under study are not relative to the rate of their oxidation in the enzymatic system.