Enhancement Of Mutagenic Activity Research Articles

Activity profiles of antimutagens: in vitro and in vivo data

In this review, retinol, chlorophyllin, and N-acetylcysteine are examined and compared with regard to their antimutagenic activity against some promutagens and a group of direct-acting alkylating agents. The promutagens included aflatoxin B 1, certain polycyclic aromatic hydrocarbons (e.g., benzo[ a]pyrene), and certain heterocyclic amines (e.g., food pyrolysates). Results of antimutagenicity testing selected from data surveyed in the published literature are displayed graphically as activity profiles of antimutagens showing both the doses tested and the extent of inhibition or enhancement of mutagenic activity. All three antimutagens are discussed in terms of their putative mechanisms of action in vitro and in vivo with emphasis on the xenobiotic metabolizing enzyme systems.

Antimutagenicity profiles of some natural substances

Selected antimutagenicity listings and profiles have been prepared from the literature on the antimutagenicity of retinoids and the carotenoid β-carotene. The antimutagenicity profiles show: (1) a single antimutagen (e.g., retinol) tested in combination with various mutagens or (2) antimutagens tested against a single mutagen (e.g., aflatoxin B 1). Data are presented in the profiles showing a dose range for a given antimutagen and a single dose for the corresponding mutagen; inhibition as well as enhancement of mutagenic activity is indicated. Information was found in the literature on the testing of selected combinations of 16 retinoids and carotenoids vs. 33 mutagens. Of 528 possible antimutagen-mutagen combinations, only 82 (16%) have been evaluated. The most completely evaluated retinoids are retinol (28 mutagens), retinoic acid and retinol acetate (7 mutagens each), and retinal and retinol palmitate (6 mutagens each). β-Carotene is the most frequently tested carotenoid (15 mutagens). Of the remaining retinoids and carotenoids, 8 were evaluated in combination with a single mutagen and the other 2 were tested against only 2 or 3 mutagens. Most of the data on antimutagenicity in vitro are available for S. typhimurium strains TA98 and TA100. Substantial data also are available for sister-chromatid exchanges in vitro and chromosome aberrations in vitro and in vivo. This report emphasizes the metabolic as well as the antimutagenic effects of retinoids in vitro and in vivo.

Enhancement of mutagenic activity in Salmonella by boiling-water extracts of Bupleuri radix

Enhancement of mutagenic activity in Salmonella by boiling-water extracts of Bupleuri radix

Occupational handling of cytostatic drugs.

The bacterial fluctuation test and measurement of the frequency of sister chromatid exchanges were used for evaluation of the exposure of different groups of hospital personnel to cytostatic drugs. Increased mutagenic activity in the urine was detected only in personnel working with inadequate safety precautions, e.g., lack of a ventilated safety cabin for preparation of parenteral solutions. Although such a safety cabin was used within the hospital pharmacy, increased mutagenic activity was detected in the urine of prescriptionists preparing parenteral cytostatic drugs. After a change of glove material and improvement of ventilation in the safety cabin, no work-related increase in urinary mutagenic activity was seen. None of the different groups tested, showed any increase in the frequency of sister chromatid exchanges. It is therefore concluded that handling of cytostatic drugs according to the issued safety recommendations including working in a well ventilated safety cabin, will not result in any enhancement of mutagenic activity in the urine related to work.

Enhancement of mutagenic activity in Salmonella by contraceptive steroids

Two oral contraceptive steroids, mestranol and norethynodrel, were evaluated for mutagenicity in the Salmonella histidine reversion assay. The pure forms of the hormones were not mutagenic when tested with either missense (TA1535, TA100) or frameshift (TA98, TA1538, TA1537) strains. In vitro activation of the hormones with liver homogenates from rats induced either with phenobarbital or Aroclor did not influence these results. However, mestranol was capable of enhancing the mutation yield obtained by an ineffective subthreshold dose of 2-acetylaminofluorene. Dimethyl sulfoxide extracts of two contraceptive pills, Ovulen-21 (containing mestranol) or Enovid-E (containing mestranol or norethynodrel), also were nonmutagenic. But again, both these extracts were capable of enhancing the mutation yield induced with an ineffective dosage of 2-acetylaminofluorene and N-nitrosopiperidine. These studies point to the possible promotional effect and subsequent potential hazard to the female consumers who use these hormones as a means of pregnancy control.