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Biomedical subjects

R Tarone

Publications and source records attributed to R Tarone.

28 records · Page 2Linked to original sources

A study of lobular carcinoma of the breast based on the Third National Cancer Survey in The United States of America.

Cases in in situ and infiltrating lobular carcinoma of the breast reported in the Third National Cancer Survey were reviewed according to age, sex, race, and geographic distribution. The age-specific incidence rates indicate that there are two peak age periods of risk for invasive lobular carcinoma, the first occurring in ages 40-50 years and the second after age 65. The incidence rates for lobular carcinoma were compared to the incidence rates for intraductal and infiltrating ductal carcinoma reported from the Third National Cancer Survey and for total breast cancer from the Miyagi prefecture in Japan. These comparisons indicate that factors which influence the geographic variation in breast cancer play important roles in the etiology of infiltrating ductal carcinoma, but may have little effect upon the incidence of lobular carcinoma and intraductal carcinoma. The limitations of large histological epidemiological surveys are discussed.

Adult↗

An epidemiologic study of cancer of the cervix, vagina, and vulva based on the Third National Cancer Survey in the United States.

Cases of invasive and in situ carcinoma of the lower female genital tract as reported in the Third National Cancer Survey in the United States were analyzed according to age, race, and geographic distribution. Results indicate that the incidence rates of in situ and invasive carcinoma of the cervix were greater in black than in white women, with a relative risk rate for black women of approximately two for both types of cervical carcinoma. For white women, the age-specific rates for invasive carcinoma of the cervix remained relatively constant after age 45, while for black women the age-specific rates for invasive carcinoma continued to increase after age 45. For both races, the patterns of age-specific incidence rates for in situ and invasive carcinoma of the cervix were not similar to those for carcinoma of the vagina or vulva. The pattern of age-specific incidence rates of adenocarcinoma of the cervix did not resemble those for in situ or invasive squamous cell carcinoma of the cervix. The rates for adenocarcinoma of the cervix demonstrated patterns similar to those for intraductal carcinoma of the breast. Results of the study are discussed in relationship to the field theory of carcinogenesis as developed for the lower female genital tract.

Adenocarcinoma↗

Development of an assay for aryl hydrocarbon (benzo(a)pyrene) hydroxylase in human peripheral blood monocytes.

An assay has been developed and measurements of aryl hydrocarbon [benzo(a)pyrene] hydroxylase have been made in peripheral blood monocytes from a human population. Treatment with benz(a)anthracene in cell culture increased aryl hydrocarbon hydroxylase activity from 6.5 to 37-fold in monocytes from each of 25 apparently healthy donors. A weak correlation (r = 0.38) was observed between the induction ratios obtained with monocytes and lymphocytes from the same donors. Reproducibilities of the monocyte and lymphocyte assays were comparable. In monocytes, the measurement of basal and induced aryl hydrocarbon hydroxylases activity does not require pretreatment with mitogens as is the case with lymphocytes. Monocytes also exhibit a much wider range of induction ratios than do lymphocytes.

Adult↗

Malignant conversion of mouse skin tumours is increased by tumour initiators and unaffected by tumour promoters.

Multi-stage carcinogenesis (initiation-promotion) was first demonstrated in mouse skin. The first stage, initiation, is accomplished by a low dose of carcinogen that causes no tumours. Promotion by repeated treatment of initiated mice with certain non-carcinogenic hyperplastic agents results in the rapid production of numerous benign papillomas, a few of which progress to squamous cell carcinomas. Although this models system produces mostly benign tumours, many of the concepts concerning carcinogenesis in epithelial tissues have been derived from mouse skin studies. The permanent change in growth potential accomplished by tumour initiators is generally considered to be a mutagenic event; cell selection and clonal expansion of initiated cells may be involved in promotion. In initiation-promotion experiments, more than 90% of the squamous cell carcinomas develop from papillomas, but the conversion rate is low. The factors necessary for this conversion of benign to malignant tumours have not been defined but tumour promoters have been assumed to be involved. However, we report here that the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) is ineffective in the conversion of papillomas to carcinomas whereas three initiators, urethane, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline-N-oxide (4-NQO) are effective. This suggests that malignant conversion may result from a further genetic change in papilloma cells and that the ineffectiveness of TPA may be due to its inactivity as a mutagen.

Animals↗

Herbicides and adjuvants: an evolving view.

The present report examines the in vitro genotoxicity (micronucleus assay) of herbicides and adjuvants and reports on an in vivo human study on potential endocrine effects of pesticides, including herbicides. Adjuvants are used in conjunction with 2,4-dichlorophenoxy acetic acid (2,4-D) and other herbicides. Earlier pesticide applier survey results (n = 709) show that 59% of the applicators used adjuvants, and the majority of this group used paraffinic oils and/or surfactant mixtures. As a beginning effort to explore the role of adjuvants and herbicides in hormonally based reproductive effects, a prospective, controlled study was performed to analyze blood specimens from three different exposure groups (applicators using herbicides only; applicators using both herbicides and insecticides; and applicators using fumigants in addition to herbicides and insecticides; and a control group composed of other agricultural workers including organic farmers). The applicators and controls were age- and smoking-matched. Study subjects (n = 78) were tested before, during, and after completion of pesticide application season for the effects of pesticide products on hormone levels in the bloodstream. Of the applicator exposure groups examined, only the herbicide group showed significant endocrinologic differences from controls. Free testosterone levels were significantly elevated in post-season measurements (p = 0.032), and follicle-stimulating hormone (FSH) was significantly decreased at the height of the season (p = 0.016) and in the post-season (p = 0.010) as compared to controls. These endocrinologic findings are discussed in terms of their possible relationship to potential endocrine effects of herbicides, herbicide contaminants, and adjuvants. In vitro genotoxicity examination compared four different commercially available surfactant mixtures with 12 different commercial herbicide products, including six different chlorophenoxy herbicides. Only one herbicide yielded a significant dose-response curve. All four adjuvants showed positive dose-response effects. These preliminary data suggest that adjuvants are not inert but are toxicologically active components added to herbicide mixtures. Whether adjuvant toxicant effects are additive or are independent of herbicide effects is poorly understood.

Adult↗

Chromosome rearrangements in fumigant appliers: possible relationship to non-Hodgkin's lymphoma risk.

Appliers of pesticides (n = 18) who are exposed to the fumigant phosphine or who have a mixed exposure to other pesticides and phosphine demonstrate a significant increase in chromosome rearrangements in G-banded chromosomes from peripheral blood compared to control subjects (n = 26). Appliers who had discontinued using phosphine for at least 8 months prior to specimen collection (n = 5) do not demonstrate significant increases in chromosome rearrangements compared to controls. Breakpoint analysis of 6,138 metaphases from all subjects demonstrates 196 breaks per 3605 metaphases in exposed subjects and 102 breaks per 2,533 metaphases in control subjects. Bands with significantly more breaks than expected based on band length in all study subjects were 1q32, 3p14, 7p15, and 14q11. Three of these four bands had significantly more breaks than expected in the exposed group, and all four bands had a significant excess of breaks in the control group. There are four bands with a significant excess of breaks in the exposed group and no breaks in the control group; each of these occurs in a known protooncogene region. These are 1p13 (NRAS), 2p23 (NMYC), 14q32 (ELK2), and 21q12 (ETS-2). Most breaks at bands 1p13, 14q32, and 21q22 are associated with chromosome rearrangements and occurred in appliers who have a mixed exposure to phosphine and other pesticides. Cytogenetic abnormalities, i.e., rearrangements and/or deletions involving bands 1p13, 2p23, and 14q32, are associated with non-Hodgkin's lymphoma. We speculate that these findings could relate to the risk of evolution of a neoplastic clone in these workers. Epidemiological studies of similarly exposed workers indicate an excess of non-Hodgkin's lymphoma.

Chromatids↗

Recognition and classification of clinically dysplastic nevi from photographs: a study of interobserver variation.

The recognition of dysplastic nevi from photographs can aid in population surveys of nevi and in epidemiological studies of melanoma risk. The reproducibility of techniques for recognizing nevi as dysplastic or for scoring them according to the degree of dysplasia has not been measured. Using photographs of 300 nevi taken in the course of a case-control study of melanoma, we assessed the agreement among six clinicians in independently categorizing nevi as dysplastic and in grading the degree of dysplasia. On average, reviewers agreed with each other 77% of the time in classifying a nevus as dysplastic or normal. Pairwise agreement within one point on a six-point scale occurred 87% of the time on average. These results suggest that criteria for recognizing nevi as clinically dysplastic from photographs can be applied reproducibility.

Analysis of Variance↗