Antioxidants and cancer. IV. Initiating activity of malonaldehyde as a carcinogen.
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Biomedical subjects
Publications and source records attributed to R J Shamberger.
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Blood leukocyte cultures were incubated with antioxidants and the carcinogens sodium cyclamate and 7,12-dimethylbenz(alpha)anthracene in different combinations. There were 17.4% more chromosomal breaks in the group of cells treated with dimethylbenzanthracene only than in the untreated controls. The reductions in chromosomal breaks by the antioxidants were as follows: ascorbic acid, 31.7%; butylated hydroxytoluene, 63.8%; Na(2)SeO(3), 42.0%; and dl-alpha-tocopherol, 63.2%. Multiple chromosomal breaks were distributed equally throughout the experimental groups. Sodium cyclamate had only slightly more chromosomal breaks than the controls (11.6 compared to 10.9%). In the cyclamate groups treated with Na(2)SeO(3), 11.2% of chromosomes were broken. More acrocentric-type chromosomal breaks (21.7%) were seen in the untreated cells than the cells treated with cyclamate (3.4%) or dimethylbenzanthracene alone (4.8%). The carcinogen-treated groups had a higher percentage of meta breaks than the untreated controls.
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Rat mammary tumours induced by 7,12-dimethylbenz[a]anthracene can undergo repeated growth and regression during successive pregnancies. In a 10-day period after birth about half of the tumours regressed 50% or more. The concentrations of the lysosomal enzymes increased in regressing mammary tumours to the following multiples of the initial values: beta-glucuronidase, 7.7; beta-galactosidase, 3.9; cathepsin, 2.9; acid ribonuclease, 2.1; arylsulphatase A, 1.5; acid phosphatase, 1.4. In contrast, several non-lysosomal enzymes failed to increase. Activities in the post-partum uterus increased to the following multiples of the initial values: beta-glucuronidase, 5.8; cathepsin, 5.5; acid ribonuclease, 4.3; beta-galactosidase, 2.2; acid phosphatase, 1.8. Arylsulphatase A in the post-partum uterus decreased significantly, suggesting a non-lysosomal distribution or a special function related to pregnancy. No other significant changes were observed in the lysosomal or non-lysosomal enzymes in the hormone-independent liver or hormone-dependent normal mammary gland. The ratio of free to bound arylsulphatase A and acid ribonuclease decreased slightly 1-3 days after birth because of problems in homogenizing the tumours. At days 4-8, however, there was a dramatic increase in the ratio of the free to bound activities. The results can be explained in terms of the lysosomal theory of intracellular digestion.
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