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Cells lacking mismatch repair (MMR) exhibit elevated levels of spontaneous mutagenesis. Evidence exists that MMR is involved in repair of some DNA lesions besides mismatches. If some oxidative DNA lesions are substrates for MMR, then the excess mutagenesis in MMR(-) cells might be blocked by dietary antioxidants. Effects of the dietary antioxidants ascorbate, alpha-tocopherol, (-)-epigallocatechin gallate (EGCG) and lycopene on spontaneous mutagenesis were studied using mismatch repair-deficient (hMLH1(-)) human colon carcinoma HCT116 cells and HCT116/ch3 cells, in which normal human chromosome 3 has been added to restore mismatch repair. HCT116 cells have a 22-fold higher spontaneous mutation rate compared with HCT116/ch3 cells. HCT116 cells cultured in 1% fetal bovine serum (FBS) have twice the spontaneous mutation rate of those cultured in 10% FBS, most likely due to reduction in serum antioxidants in the low serum medium. As expected, alpha-tocopherol (50 microM) and ascorbate (284 microM) reduced spontaneous mutagenesis in HCT116 cells growing in 1% serum more dramatically than in cells cultured in 10% serum. The strongest antimutagenic compound was lycopene (5 microM), which reduced spontaneous mutagenesis equally (about 70%) in HCT116 cells growing in 10 and 1% FBS and in HCT116/ch3 cells. Since lycopene was equally antimutagenic in cells growing in low and high serum, it may have another antimutagenic mechanism in addition to its antioxidant effect. Surprisingly, EGCG (10 microM) was toxic to cells growing in low serum. It also reduced spontaneous mutagenesis equally (nearly 40%) in HCT116 and Petition to Include Synthetic Crystalline LYCOPENE at 7 CFR 205.605 HCT116/ch3 cells. The large proportion of spontaneous mutagenesis that can be blocked by antioxidants in mismatch repair-deficient cells support the hypothesis that a major cause of their excess mutagenesis is endogenous oxidants. Blocking spontaneous mutagenesis, perhaps with a cocktail of antioxidants, should reduce the risk of cancer in people with a genetic defect in mismatch repair as well as other individuals. 8 11. Research information about the substance which includes comprehensive substance research reviews and research bibliographies. The following information is taken from a USDA Agricultural Research Service news release originating from the Grand Forks Human Nutrition Research Center: 9 Tomato's red hue comes mainly from a phytochemical called lycopene, a compound appearing to act as an anti-oxidant and neutralizing free radicals that damage cells of our body. Studies revealed that eating tomato may reduce the risk of cancer. In a study of over 40,000 health professionals, Harvard investigators reported that men who ate more than 10 servings of tomato-based foods daily could cut the risk of developing prostate cancer by 35 percent compared to those who ate the least amount of these foods. The benefits of lycopene were even more pronounced with advanced stages of prostate cancer. In another study of prostate cancer, researchers analyzed blood levels of lycopene and found that the risk of developing prostate cancer decreased with increased blood lycopene levels. The high level of lycopene in the blood was associated with low blood levels of prostate specific antigen, a biomarker of prostate health. Furthermore, studies indicated that tomato consumption may reduce the risk of colorectal, stomach and lung cancers. A greater intake of lycopene-rich tomato may benefit heart health by lowering the risk of cardiovascular disease. Studies showed that tomato lycopene prevented the oxidation of LDL "bad" cholesterol. In the process known as atherosclerosis, LDL cholesterol, fat and other substances are deposited in the arteries as plaque. When plaque builds up over time, it narrows the inner artery making it harder for blood to flow. Low levels of lycopene in blood are associated with increased mortality from heart disease (compared with higher levels). A clinical study showed that eight weeks of daily intake of a tomato extract was related to a significant drop in both systolic and diastolic blood pressure in patients with mild to moderate hypertension. The investigators assumed that this antihypertensive effect is a result of the antioxidative activity of the tomato extract. A comprehensive review entitled “Carotenoids: Actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans,” was recently published in 2009 in the journal Molecular Nutrition and Food Research 10 . This review is available in Appendix F. 8 http://tools.niehs. nih.gov/portfolio/index.cfm? action=portfolio.publicationdetail&id=323863. Accessed June 1, 2011. 9 http://www.ars. usda.gov/News/docs.htm? docid=19428 . Accessed June 1, 2011. 10 Mol. Nutr. Food Res. 2009, 53, S194 –S218. Petition to Include Synthetic Crystalline LYCOPENE at 7 CFR 205.605 12. A „„Petition Justification Statement‟‟ which provides justification for inclusion of lycopene on the National List, §205.605(b) Human colostrum and human milk contain carotenoids, including lycopene. Sommerburg et al. 11 reported that lycopene levels in colostrum – 121 mcg/L – were four times higher than in mature human milk – 32 mcg/L. Patton et al. 12 found that human colostrum contained 960 mcg/L of lycopene. Several researchers have reported on the lycopene content of mature human milk. Reported values vary from 10 mcg/L 13 to 17 mcg/L 14 , 26 mcg/L 15 , 27mcg/L 16 , and as high as 93 mcg/L 17 . Including tomato sauce, a very bioavailable food source of lycopene, in the lactating woman’s diet increased the lycopene content of her milk by 24 mcg/L within 3 days 12 . Term infants are born with measurable plasma lycopene levels that further increase when they are fed human milk after birth 13 . Unless an infant formula is deliberately fortified with lycopene, it will contain virtually none of this carotenoid. Sommerburg et al. 18 analyzed eight infant formula preparations and found no measurable lycopene in any of them. They observed that plasma lycopene levels in infants fed these infant formulas declined to low and even non-detectable levels within two weeks after