Ranking Possible Carcinogenic Hazards

Ames, Bruce N.; Magaw, Renae; Gold, Lois Swirsky

doi:10.1126/science.3563506

Cited by 547 publications

(168 citation statements)

References 114 publications

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“…Possible hazards from residues of synthetic chemicals should be routinely compared to the possible hazards from natural chemicals. We have found that when the same index is used for natural and synthetic chemicals, possible carcinogenic hazards from current levels of pesticide residues or water pollution are likely to be of minimal concern relative to the background levels of natural substances (117,118 …”

Section: Dna Repair and Other Inducible Defensesmentioning

confidence: 99%

DNA lesions, inducible DNA repair, and cell division: three key factors in mutagenesis and carcinogenesis.

Ames

Shigenaga

Gold

1993

Environ Health Perspect

268

155

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DNA lesions that escape repair have a certain probability of giving rise to mutations when the cell divides. Endogenous DNA damage is high: 106 oxidative lesions are present per rat cell. An exogenous mutagen produces an increment in lesions over the background rate of endogenous lesions. The effectiveness of a particular lesion depends on whether it is excised by a DNA repair system and the probability that it gives rise to a mutation when the cell divides. When the cell divides, an unrepaired DNA lesion has a certain probability of giving rise to a mutation. Thus, an important factor in the mutagenic effect of an exogenous agent whether it is genotoxic or non-genotoxic, is the increment it causes over the background cell division rate (mitogenesis) in cells that appear to matter most in cancer, the stem cells, which are not on their way to being discarded. Increasing their cell division rate increases mutation and therefore cancer. There is little cancer from nondividing cells. Endogenous cell division rates can be influenced by hormone levels, decreased by calorie restriction, or increased by high doses of chemicals. If both the rate of DNA lesions and cell division are increased, then there will be a multiplicative effect on mutagenesis (and carcinogenesis), for example, by high doses of a mutagen that also increases mitogenesis through cell killing. The defense system against reactive electrophilic mutagens, such as the glutathione transferases, are also almost all inducible and buffer cells against increments in active forms of chemicals that can cause DNA lesions. A variety of DNA repair defense systems, almost all inducible, buffer the cell against any increment in DNA lesions. Therefore, the effect of a particular chemical insult depends on the level of each defense, which in turn depends on the past history of exposure. Exogenous agents can influence the induction and effectiveness of these defenses. Defenses can be partially disabled by lack of particular micronutrients in the diet (e.g., antioxidants). Four endogenous processes leading to significant DNA damage are oxidation (1-3), methylation, deamination, and depurination (2). The importance of these processes is supported by the existence of specific DNA repair glycosylases for oxidative, methylated, and deaminated adducts and a repair system for apurinic sites that are produced by spontaneous depurination (3). Endogenous DNA Damage and MutagenesisDNA damage produced by oxidation appears to be the most significant endogenous damage (4). We estimate that the DNA hits per cell per day from endogenous oxidants are normally 105 in the rat and 104 in the human (5-7). These oxidative lesions are effectively but not perfectly repaired; the normal steady-state level of oxidative DNA lesions is about 106 per cell in the young rat and about twice this in the old rat (6,8). Oxidants are produced as byproducts of mitochondrial electron transport, various oxygen-utilizing enzyme system, peroxisomes, and other processes associated with normal aerobic metabolism...

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Section: Dna Repair and Other Inducible Defensesmentioning

confidence: 99%

DNA lesions, inducible DNA repair, and cell division: three key factors in mutagenesis and carcinogenesis.

Ames

Shigenaga

Gold

1993

Environ Health Perspect

268

155

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“…As an example of this approach, Ames et al (1987) compared the potential carcinogenic hazard of selected naturally occurring and man-made chemicals in the environment using a human exposure dose/rodent potency dose (HERP) index that relates the potency of carcinogens in rodents to the exposure in humans (see Figure 10). These authors found that with regard to dietary exposures, a number of ''natural pesticides'' or ''natural toxic chemicals'' were present at higher concentrations in food and had similar or greater cancer potencies than some common man-made pesticides or chemicals.…”

Section: Comparisons To Background Levels Of Riskmentioning

confidence: 99%

“…Third, they can be used to illustrate how a particular indicator or biomarker of exposure is either appropriate or inappropriate for evaluating risks from a specific source, depending on whether measured exposure levels are distinguishable from background. All of these approaches provide additional information on the magnitude (and ultimately acceptability) of a particular chemical exposure or health risk or the usefulness of certain types of data.As an example of this approach, Ames et al (1987) compared the potential carcinogenic hazard of selected naturally occurring and man-made chemicals in the environment using a human exposure dose/rodent potency dose (HERP) index that relates the potency of carcinogens in rodents to the exposure in humans (see Figure 10). These authors found that with regard to dietary exposures, a number of ''natural pesticides'' or ''natural toxic chemicals'' were present at higher concentrations in food and had similar or greater cancer potencies than some common man-made pesticides or chemicals.…”

mentioning

confidence: 99%

Health risk communication using comparative risk analyses

Williams¹

2004

J Expo Sci Environ Epidemiol

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The ability to communicate effectively the degree or magnitude of public exposures or health risks is essential for risk assessors and risk managers. Various guidelines exist for communicating environmental and public health risks, including recommended approaches for putting risk data into proper context. Although it remains unclear as to which approach is the most useful or appropriate under different circumstances, risk comparisons are a popular choice for conveying the significance of or providing a better perspective on a particular chemical exposure or health risk. In this paper, several different types of risk comparisons are described that are frequently used in the private and public sectors, and these are illustrated using a variety of examples from the literature. These approaches include: (1) intrachemical comparisons, (2) interchemical comparisons, (3) comparisons to background levels of risk, (4) comparisons to theoretical risks or safety levels, and (5) comparisons to other actions or activities. The primary purpose of this paper is to summarize and briefly discuss the advantages and limitations of these risk communication approaches. The evolving field of risk communication is also discussed, including ongoing research on public risk perceptions and alternative methods for communicating risk magnitudes and data uncertainties. Journal of Exposure Analysis and Environmental Epidemiology IntroductionThe ability to communicate effectively the degree or magnitude of public exposures or health risks is essential for risk assessors and risk managers (Williams, 2000). Risk communication is the process of conveying information about an exposure, risk, or risk management decision (NRC, 1989). More specifically, risk communication can be defined as ''any public or private communication that informs individuals about the existence, nature, severity, or acceptability of risks '' (Plough and Krimsky, 1987). Communicating risks often involves interpreting available scientific evidence, and describing and summarizing scientific knowledge about exposure and risk issues (NRC, 1989). Risk communication can also be used to influence public opinion or choice, or to arouse or alleviate public concerns about a risk issue (Kasperson et al., 1988;Sandman, 1993). The history of risk communication as applied to environmental and public health risks has not been fully documented, but has clearly evolved through several developmental stages over time (Fischhoff, 1995) and may have been influenced by the desire to gain acceptance for decisions grounded in risk assessment methods (Plough and Krimsky, 1987) or the organizational adaptation of chemical manufacturers to external pressures (Chess, 2001).Over the last 20 years, various guidelines have been published for communicating environmental and public health risks. For example, the Agency for Toxic Substances and Disease Registry (ATSDR) has produced several risk communication reports and case studies as part of their mission to explain the public health hazards associated...

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“…As Ames et al recently pointed out, we need better measures of both risk and "anti-risk" factors for cancer. 37 Direct evidence of human cancer risk is derived from epidemiologic investigations and clinical observations. Table 4 shows six general approaches to delineating the environmental or occupational etiologies of human cancer, ranging from complex designs such as the cohort study or case control study, to simpler approaches, such as mathematical modelling and ecologic or correlational studies.…”

Section: Methods and Measures For Identifying Occupationalmentioning

confidence: 99%

Cancer prevention in the workplace and natural environment a review of etiology, research design, and methods of risk reduction

Swanson¹

1988

Cancer

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Guidelines for developing programs in cancer prevention and reduction of risk related to occupational and environmental carcinogens are provided in this review, which includes a summary of experimental and epidemiologic research designs for assessing potential etiologic agents, an overview of known occupational and environmental carcinogens, and a summary of general approaches to risk reduction. This review includes human cancer risks in the workplace and in the natural environment, which encompasses air pollution, water pollution, and hazardous waste disposal. Fourteen tables present the following: (1) established and probable carcinogens that may be encountered in the workplace, as contaminants of air or water, or as hazardous waste; (2) regulated carcinogens; (3) primary sources of exposure; (4) research designs; and (5) risk reduction methods. The interactive effects of multiple exposures are discussed as they relate to etiology and prevention. The importance of federal regulation is emphasized, as well as the need to understand the potential for cancer prevention in the context of broader economic, political and social issues.

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Ranking Possible Carcinogenic Hazards

Cited by 547 publications

References 114 publications

DNA lesions, inducible DNA repair, and cell division: three key factors in mutagenesis and carcinogenesis.

DNA lesions, inducible DNA repair, and cell division: three key factors in mutagenesis and carcinogenesis.

Health risk communication using comparative risk analyses

Cancer prevention in the workplace and natural environment a review of etiology, research design, and methods of risk reduction

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