Interspecies comparisons of tissues DNA damage, repair, fixation, and replication

Journal Article · Fri Apr 01 04:00:00 EST 1988 · Environ. Health Perspect.; (United States)

DOI:https://doi.org/10.1289/ehp.887773· OSTI ID:6219209

Slaga, T J

The many anatomical, physiological, and biochemical differences among various mammalian species make it difficult to extrapolate carcinogenic potency data from animals to humans. The process is further complicated by the multistep origin of most malignant tumors in animals and humans due to the interaction of target cells with both endogenous and exogenous factors. Species differences in these aspects of carcinogenesis must also be considered when attempting to evaluate the carcinogenic risks of chemicals to humans. Cancer development in animals involves at least three distinct stages: initiation, promotion, and progression. Intra- and interspecies differences in susceptibility to carcinogenesis may be related to any one or a combination of these stages. Variation in species susceptibility to tumor initiation may result from differences in the abilities of various species to metabolize a potential carcinogen to an ultimate carcinogenic form and/or to detoxify the carcinogen. Most comparative studies among species have only revealed subtle differences in metabolism. DNA adducts from several activated carcinogens have been found to be the same in a number of tissues from various species, including humans. Capacity for DNA repair is apparently a critical factor in the initiation of carcinogenesis in target cells of different species but is less critical among mice that differ in susceptibility to two-stage carcinogenesis of the skin and liver. Susceptibility variations among stocks and strains to such carcinogenesis appear to be related to alterations in tumor promotion. Additional comparative studies are critically needed on all aspects of carcinogenesis to permit effective extrapolation of carcinogenic potency data from animals to humans.

• Research Organization: Univ. of Texas System, Smithville (USA)
• OSTI ID: 6219209
• Journal Information: Environ. Health Perspect.; (United States), Journal Name: Environ. Health Perspect.; (United States) Vol. 77; ISSN EVHPA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
560300 -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
AFLATOXIN
AMINES
ANIMALS
ANTIGENS
AROMATICS
BENZOPYRENE
BIOLOGICAL PATHWAYS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
CARCINOGEN SCREENING
CARCINOGENESIS
CONDENSED AROMATICS
DIGESTIVE SYSTEM
DNA ADDUCTS
DNA REPAIR
DOGS
ENZYME ACTIVITY
GLANDS
HYDROCARBONS
LABELLED COMPOUNDS
LIVER
MAMMALS
MAN
MATERIALS
METABOLIC ACTIVATION
MICE
NITROSAMINES
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
POLYCYCLIC AROMATIC HYDROCARBONS
PRIMATES
PROMOTERS
RABBITS
RECOVERY
REPAIR
RODENTS
SCREENING
SKIN
SPECIES DIVERSITY
TOXIC MATERIALS
TOXINS
TRITIUM COMPOUNDS
TUMOR PROMOTERS
VERTEBRATES