Mechanisms, chemical carcinogenesis, and risk assessment: Cell proliferation and cancer

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Abstract
Mechanisms of carcinogenesis—and in particular chemically associated carcinogenicity—have attracted considerable scientific and public attention in the last decade. Much insight has been gained that will lead to more reasoned and better prevention, intervention, and treatment for the reduction of environmentally caused cancers. However, there seems to be an exaggerated tendency to embrace “mechanisms” not yet fully characterized, completely tested, unequivocally proven, and consensus accepted. More than 100 agents and exposure circumstances have been identified as causally or strongly associated with human cancers; for many the evidence was discovered first in experimental animals. More chemicals have been uncovered as carcinogenic in experimental animals, with as yet no or little available information in exposed human populations. Additional and expanded mechanistic and epidemiological studies should further elucidate the relevance of these agents to adverse human health effects, including cancers. Claims are being posed that certain chemical‐specific “mechanisms” in experimental systems are irrelevant to humans, and thus chemicals thought to be aberrantly carcinogenic in animals would present no cancer hazard to exposed humans. Nonetheless before undeniable proof becomes available, we must continue to proceed with sensitive and responsible caution. This commentary offers a central and personal view of one such mechanism: cell proliferation and cancer.