Oxidative damage to sperm DNA: smoking and diet interaction

Institution:	Children's Hospital Oakland Research Institute
Investigator(s):	Bruce Ames, Ph.D.
Award Cycle:	1998 (Cycle 7)	Grant #: 7RT-0178A	Award: $132,367
Subject Area:	General Biomedical Science
Award Type:	Research Project Awards

Abstracts

Final Report

Our objectives were 1) to quantify damage to sperm from harmful compounds in cigarette smoke, 2) to determine how smoking affects antioxidant compounds in the body, 3) to determine the negative impact of smoking on folic acid and vitamin B-12 metabolism, and consequent damage to DNA, and 4 & 5) to investigate the impact of smoking on various vitamin E forms in the body. We have discovered that, when the diet of smokers is equal to the diet of nonsmokers, the only circulating antioxidant that is depleted is vitamin C. This finding was published during this grant-funding period and was also used by the National Academy of Sciences to justify setting a separate requirement for vitamin C for smokers. We have also found that men who typically consume diets low in fruits and vegetables can increase their circulating vitamin C levels by consuming a combined vitamin supplement containing modest amounts of vitamin C, E and folic acid. This same supplement also increased the ratio of one form of vitamin E, alpha-tocopherol to another form, gamma-tocopherol in the blood. We do not understand the significance of this result yet, because there is presently no established biological role for gamma-tocopherol. We have assessed oxidative damage to circulating lipids and proteins using various methods. Thus far, we have found no differences due to smoking and/or combined vitamin supplementation. We expect to complete a draft of a paper this year describing these findings. We are continuing methods development work on sperm DNA extraction and DNA damage assessment (8-oxoguanine) techniques. We have also published a paper showing that folic acid metabolism is impaired in men who smoke; we think that could be due to a inactivation of vitamin B-12 by the NOx in cigarette smoke. Vitamin B12 deficiency causes chromosome breaks in humans. We also showed that low folic acid in seminal fluid is associated with low sperm count and quality in both smokers and non-smokers. This information will help health professionals understand how smoking negatively impacts nutrition and health, and will also help experts set nutrition requirements for minimizing the negative effects of smoking. Additionally, this work furthers the understanding of basic scientists regarding the mechanisms by which cigarette smoking causes cancer.

Publications

Ascorbate is preferentially depleted by smoking and repleted by supplementation: a study in male smokers and nonsmokers with similar dietary antioxidant intakes
Periodical: American Journal of Clinical Nutrition			Index Medicus:
Authors: Lykkesfeldt J, Christen S, Wallock LM, Chang HH, Jacob RA, Ames BN				ART
Yr: 2000	Vol: 71	Nbr:	Abs:	Pg: 530-736

Cancer prevention and diet: help from SNPs
Periodical: Proceedings of the National Academy of Sciences of the United States of America			Index Medicus:
Authors: Ames BN				ART
Yr: 1999	Vol: 70	Nbr:	Abs:	Pg: 12216-12218

Low seminal plasma folate is associated with low sperm density and number in smoking and nonsmoking men
Periodical: Fertility and Sterility			Index Medicus:
Authors: Wallock LM, Tamura T, Mayr CA, Johnston KE, Ames BN, Jacob RA				ART
Yr: 2001	Vol: 75	Nbr:	Abs:	Pg: 252-259

N-t-Butyl hydroxylamine is an antioxidant that reverses age-related changes in mitochondria
Periodical: FASEB Journal			Index Medicus:
Authors: Atamna H, Robinson C, Ingersoll R, Ames BN				ART
Yr: 2001	Vol: 15	Nbr:	Abs:	Pg: 2196-2204

DNA damage from micronutrient deficiencies is likely to be a major cause of cancer
Periodical: Mutation Research			Index Medicus:
Authors: Ames BN				ART
Yr: 2001	Vol: 475	Nbr:	Abs:	Pg: 7-20

Ascorbate is preferentially depleted by smoking and repleted by supplementation: a study in male smokers and nonsmokers with similar dietary antioxidant intakes
Periodical: American Journal of Clinical Nutrition			Index Medicus:
Authors: Lykkesfeldt J, Christen S, Wallock LM, Chang HH, Jacob RA, Ames BN				ART
Yr: 2000	Vol: 71	Nbr:	Abs:	Pg: 530-736

Cancer prevention and diet: help from SNPs
Periodical: Proceedings of the National Academy of Sciences of the United States of America			Index Medicus:
Authors: Ames BN				ART
Yr: 1999	Vol: 70	Nbr:	Abs:	Pg: 12216-12218

Low seminal plasma folate is associated with low sperm density and number in smoking and nonsmoking men
Periodical: Fertility and Sterility			Index Medicus:
Authors: Wallock LM, Tamura T, Mayr CA, Johnston KE, Ames BN, Jacob RA				ART
Yr: 2001	Vol: 75	Nbr:	Abs:	Pg: 252-259

N-t-Butyl hydroxylamine is an antioxidant that reverses age-related changes in mitochondria
Periodical: FASEB Journal			Index Medicus:
Authors: Atamna H, Robinson C, Ingersoll R, Ames BN				ART
Yr: 2001	Vol: 15	Nbr:	Abs:	Pg: 2196-2204

DNA damage from micronutrient deficiencies is likely to be a major cause of cancer
Periodical: Mutation Research			Index Medicus:
Authors: Ames BN				ART
Yr: 2001	Vol: 475	Nbr:	Abs:	Pg: 7-20