Impaired control over drinking predicts changes in alcohol-related consequences over and above alcohol use and facets of impulsivity.

The Theory of Planned Behavior (Ajzen, 1991) states that behavioral intention is the strongest determinant of human behavior. Impaired control (IC; Heather et al., 1993) reflects an intentional failure to consume less alcohol. Cross-sectional studies suggest that IC may mediate relations between impulsivity facets and drinking outcomes but there is only one prospective study examining ICS-Failed-Control (Leeman et al., 2009) and it did not account for effects of impulsivity-facets. Our study sought to address this gap in the literature by examining ICS-Failed-Control as a mediator of relations between impulsivity facets and alcohol-related consequences. We fit a three-wave cross-lagged panel model in a sample of 448 young adults (21-23) from an alcohol challenge study with longitudinal follow-ups (6 and 12 months). Participants completed the UPPS-P, TLFB Interview, the ICS-Failed-Control scale and the YAACQ. Although IC did not mediate effects of impulsivity on alcohol consequences, IC significantly predicted changes in alcohol-related problems at the12-month follow-up, accounting for effects of UPPS-P constructs as well as alcohol use. Lack of premeditation predicted change in alcohol use from baseline to 6-month follow-up and alcohol use (at 6-months) mediated the effect of premeditation (at baseline) on alcohol consequences (at 12-months). Our findings suggest that ICS-Failed-Control is not a mediator of the effects of impulsivity but is a unique predictor of consequences. Future studies should assess UPPS-P constructs earlier in adolescence to identify potential prospective links between UPPS-P constructs and IC.

Does loneliness before the age of twelve indirectly affect impaired control over drinking, alcohol use, and problems through perceived stress?

Loneliness is the pain of feeling socially isolated from others (Russell et al., 1980). The Stress-Dampening Hypothesis (Marlatt, 1987; Sayette, 1993; Sher, 1987) posits that individuals drink to alleviate negative affect. To date, it has not been determined whether loneliness experienced as a child can indirectly influence at-risk patterns of alcohol use through the mediating mechanism of stress and impaired control. Impaired control over alcohol use (IC) is the difficulty adhering to one's own self-proscribed limits on drinking behaviors (Heather et al., 1993). Impaired control is an at-risk pattern of use that is particularly relevant to emerging adults. Methods: We examined the direct and indirect relationships between childhood loneliness, stress, IC, and alcohol-related problems with a structural equation model. In a college student sample, we utilized a (k = 20,000) bootstrap technique and a model indirect command in Mplus to examine potential mediational pathways. Cisgender sex was included as a covariate. Results: Loneliness was directly linked to stress as well as to alcohol-related problems. Higher levels of loneliness were indirectly linked to both more alcohol use and alcohol-related problems through more stress and in turn, more impaired control over drinking. Conclusions: The current study is consistent with the Stress Dampening Hypothesis (Marlatt, 1987; Sayette, 1993; Sher, 1987). Our findings suggest that therapeutic interventions combating loneliness in childhood may disrupt the stress-dampening pathway to dysregulated alcohol use in emerging adulthood.

Perfectionism and self-medication as mediators of the links between parenting styles and drinking outcomes.

OBJECTIVE: Perfectionism reflects unreasonably high expectations for oneself that are rarely obtainable leading to negative affect. The self-medication model suggests that alcohol consumption is negatively reinforced and subsequently escalated due to reductions in negative affect when drinking (Hersh & Hussong, 2009). Wang (2010) found that parents directly influence perfectionism levels. Parents have also been found to indirectly influence alcohol-related problems (Patock-Peckham & Morgan-Lopez, 2006, 2009). The current study sought to examine the indirect effects of parenting on alcohol-related problems and alcohol use quantity/frequency through perfectionism dimensions, (i.e. order, discrepancy, and high standards) depression, and self-medication motives for drinking. We hypothesized that more critical parenting and perfectionism discrepancy would be associated with heavier drinking by increasing depressive symptoms and promoting drinking for negative reinforcement. METHOD: A structural equation model with 419 university volunteers was utilized to test our mediational hypotheses. RESULTS: The analyses identified an indirect link between maternal authoritarian parenting and alcohol-related problems operating through perfectionism discrepancy. Higher levels of maternal authoritarian parenting were associated with greater perfectionism discrepancy which contributed to higher levels of depression, and in turn, stronger self-medication motives, as well as more alcohol-related problems. CONCLUSIONS: Maternal authoritarian parenting style is directly linked to perfectionism discrepancy along the self-medication pathway to alcohol-related problems. Our results suggest that the reduction of perfectionism discrepancy may be a good therapeutic target for depression as well as inform the development of parent or individual based prevention efforts to reduce risk for alcohol-related problems.

Narcissism and Devaluing Others: An Exploration of Impaired Control Over Drinking as a Mediating Mechanism of Alcohol-Related Problems.

Devaluing or diminishing the worth of others is how many individuals destroy their relationships, such as by drinking beyond limits at inappropriate times and letting others down. Impaired control over drinking (IC) reflects consuming alcohol beyond predetermined limits. This investigation sought to determine whether facets of vulnerable narcissism (e.g., entitlement-rage, hiding-the-self, contingent-self-esteem, and devaluing) or narcissistic grandiosity (e.g. grandiose-fantasy, self-sacrificing-for-self-enhancement, and exploitativeness) were directly related to IC and indirectly related to drinking outcomes. We examined a path model of 759 university student drinkers. Our results show that while grandiose-fantasy (i.e., desire for special recognition) was negatively linked to IC, devaluing was positively linked to IC. In addition, men scored higher on exploitativeness (i.e., interpersonally manipulative for personal gain) than women. We conducted mediational analysis with asymmetric confidence intervals and a bias-corrected bootstrap technique. Mediational tests showed that higher levels of grandiose-fantasy were indirectly related to fewer alcohol-related problems through less IC and less heavy-episodic drinking. In contrast, higher levels of devaluing were indirectly related to more alcohol-related problems through more IC and heavy-episodic-drinking. Our results suggest that targeting thought processes in which people with Alcohol Use Disorders (AUDs) are actively devaluing others may be a good target for therapeutic intervention.

Comparative study of the biodegradability of porous silicon films in simulated body fluid.

The biodegradability of oxidized microporous, mesoporous and macroporous silicon films in a simulated body fluid with ion concentrations similar to those found in human blood plasma were studied using gravimetry. Film dissolution rates were determined by periodically weighing the samples after removal from the fluid. The dissolution rates for microporous silicon were found to be higher than those for mesoporous silicon of comparable porosity. The dissolution rate of macroporous silicon was much lower than that for either microporous or mesoporous silicon. This is attributed to the fact that its specific surface area is much lower than that of microporous and mesoporous silicon. Using an equation adapted from [Surf. Sci. Lett. 306 (1994), L550-L554], the dissolution rate of porous silicon in simulated body fluid can be estimated if the film thickness and specific surface area are known.

Characterization of skin abnormalities in a mouse model of osteogenesis imperfecta using high resolution magnetic resonance imaging and Fourier transform infrared imaging spectroscopy.

Evaluation of the skin phenotype in osteogenesis imperfecta (OI) typically involves biochemical measurements, such as histologic or biochemical assessment of the collagen produced from biopsy-derived dermal fibroblasts. As an alternative, the current study utilized non-invasive magnetic resonance imaging (MRI) microscopy and optical spectroscopy to define biophysical characteristics of skin in an animal model of OI. MRI of skin harvested from control, homozygous oim/oim and heterozygous oim/+ mice demonstrated several differences in anatomic and biophysical properties. Fourier transform infrared imaging spectroscopy (FT-IRIS) was used to interpret observed MRI signal characteristics in terms of chemical composition. Differences between wild-type and OI mouse skin included the appearance of a collagen-depleted lower dermal layer containing prominent hair follicles in the oim/oim mice, accounting for 55% of skin thickness in these. The MRI magnetization transfer rate was lower by 50% in this layer as compared to the upper dermis, consistent with lower collagen content. The MRI transverse relaxation time, T2, was greater by 30% in the dermis of the oim/oim mice compared to controls, consistent with a more highly hydrated collagen network. Similarly, an FT-IRIS-defined measure of collagen integrity was 30% lower in the oim/oim mice. We conclude that characterization of phenotypic differences between the skin of OI and wild-type mice by MRI and FT-IRIS is feasible, and that these techniques provide powerful complementary approaches for the analysis of the skin phenotype in animal models of disease.

Carcinogenesis studies of cresols in rats and mice.

Cresols, monomethyl derivatives of phenol, are high production chemicals with potential for human exposure. The three isomeric forms of cresol are used individually or in mixtures as disinfectants, preservatives, and solvents or as intermediates in the production of antioxidants, fragrances, herbicides, insecticides, dyes, and explosives. Carcinogenesis studies were conducted in groups of 50 male F344/N rats and 50 female B6C3F1 mice exposed to a 60:40 mixture of m- and p-cresols (m-/p-cresol) in feed. Rats and mice were fed diets containing 0, 1500, 5000, or 15,000 ppm and 0, 1000, 3000, or 10,000 ppm, respectively. Survival of each exposed group was similar to that of their respective control group. Mean body weight gains were depressed in rats exposed to 15,000 ppm and in mice exposed to 3000 ppm and higher. A decrease of 25% over that of controls for the final mean body weight in mice exposed to 10,000 ppm appeared to be associated with lack of palatability of the feed. A marginally increased incidence of renal tubule adenoma was observed in the 15,000-ppm-exposed rats. The increased incidence was not statistically significant, but did exceed the range of historical controls. No increased incidence of hyperplasia of the renal tubules was observed; however, a significantly increased incidence of hyperplasia of the transitional epithelium associated with an increased incidence of nephropathy was observed at the high exposure concentration. The only significantly increased incidence of a neoplastic lesion related to cresol exposure observed in these studies was that of squamous cell papilloma in the forestomach of 10,000-ppm-exposed mice. A definitive association with irritation at the site-of-contact could not be made because of limited evidence of injury to the gastric mucosa at the time of necropsy. However, given the minimal chemical-related neoplastic response in these studies, it was concluded that there was no clear evidence of carcinogenicity in male rats or female mice exposed to the cresol mixture.

Carcinogenesis studies of benzophenone in rats and mice.

Benzophenone, an aryl ketone, is used primarily as a photoinitiator and fragrance enhancer. Groups of 50 male and 50 female F344 rats and B6C3 F1 mice were fed diets containing 0, 312, 625, and 1250 ppm benzophenone for 105 weeks. Survival of males exposed to 1250 ppm benzophenone was significantly less than that of controls. There was a positive trend in the incidence of renal tubule adenoma in male rats; these neoplasms were accompanied by significantly increased incidences of renal tubule hyperplasia. Increased incidences of mononuclear cell leukemia were observed in male rats exposed to 312 or 625 ppm benzophenone and in female rats exposed to 625 ppm benzophenone. Liver lesions observed included significantly increased incidences of hepatocytic centrilobular hypertrophy in all exposed groups of rats. In mice, survival of all exposed groups was generally similar to that of the control groups. In male mice, there were significantly increased incidences of hepatocellular adenoma in the 625 and 1250 ppm groups. In female mice, the incidences of hepatocellular adenoma in the 625 and 1250 ppm groups were higher than expected after adjusting for the lower body weights in these groups. The incidences of kidney nephropathy in exposed groups of female mice, as well as the severity of nephropathy in exposed groups of males, were significantly increased. The incidences of metaplasia of the olfactory epithelium were significantly increased in 1250 ppm mice. Rare histiocytic sarcomas were observed in female rats and mice in the 625 and 1250 ppm groups. Under the conditions of these 2-year studies, there was some evidence of carcinogenic activity of benzophenone in male F344/N rats based on increased incidences of renal tubule adenoma. There was equivocal evidence of carcinogenic activity of benzophenone in female F344/N rats based on the marginal increased incidences of mononuclear cell leukemia and histiocytic sarcoma. There was some evidence of carcinogenic activity of benzophenone in male B6C3F(1) mice based on increased incidences of hepatocellular neoplasms, primarily adenoma. There was some evidence of carcinogenic activity of benzophenone in female B6C3F(1) mice based on increased incidences of histiocytic sarcoma; the incidences of hepatocellular adenoma in female B6C3F(1) mice may have been related to benzophenone exposure.

A social learning perspective: a model of parenting styles, self-regulation, perceived drinking control, and alcohol use and problems.

BACKGROUND: This investigation sought to determine how different parenting styles are related to general self-regulatory processes that are linked to alcohol use and abuse. Self-regulation and, more specifically, thoughts of control over drinking are forms of positive self-control mechanisms. Parenting styles are known determinants of both negative and positive self-control mechanisms in offspring. According to social learning theory, stronger relationships between parenting style and self-regulatory processes would be expected from the parent who is the same sex as the respondent. METHODS: A total of 144 female and 107 male college students currently using alcohol were administered a questionnaire on their alcohol use and problems, perceived style of parenting (authoritarian, permissive, or authoritative) of their parents, self-regulation, and perceived control of drinking. A model linking parenting styles, self-regulatory processes, and control over drinking with alcohol use and alcohol problems was tested across sex groups by using structural equation modeling. RESULTS: In general, the parenting style of the parent of the same sex as the respondent's was found to be significantly related to self-regulation, which is known to be protective against alcohol use and abuse. A permissive parent of the same sex as the respondent was negatively associated with good self-regulatory processes for both men and women. Having an authoritative mother was also shown to be related to higher levels of self-regulation for women. CONCLUSIONS: Self-regulation mediated the pathway from a permissive parenting style to perceived drinking control, which, in turn, mediated the pathway from self-regulation to alcohol use and problems. Finally, self-regulation mediated the positive pathway from an authoritative mother to perceived control over drinking for women.

A retrospective analysis of background lesions and tissue accountability for male accessory sex organs in Fischer-344 rats.

Because the paired lobes (ventral, dorsal, lateral, and anterior) of the rat prostate have not been consistently sampled in many carcinogenicity and toxicity studies, comparison among different investigations has been compromised. The lack of specific site identification for prostatic lesions further lessens the value of incidences reported. We present here the lobe-specific incidences and degree of severity of background prostatic, seminal vesicular, and ampullary glandular lesions in 1768 control Fischer-344 rats from 35 recent National Toxicology Program 2-year carcinogenicity and toxicity studies conducted in 4 laboratories. The dorsal and lateral lobes were combined and considered the dorsolateral lobe where inflammation, epithelial degeneration, mucinous cysts, and edema were observed. Inflammation in the dorsolateral lobes was significantly associated with pituitary gland adenoma whose prolactin was suggested to play an important role in pathogenesis of prostatic inflammation. Epithelial degeneration, epithelial hyperplasia, inflammation, edema, and adenoma were conspicuous in the ventral lobes. Inflammation and edema occurred in the anterior lobes (coagulating glands). Inflammation, dilatation, epithelial hyperplasia, edema, and adenoma were observed in the seminal vesicles. Inflammation was also present in the ampullary glands. We suggest an optimal embedment and trimming method in rat prostate and seminal vesicle to ensure adequate, consistent sampling.

Effects of alcoholic beverage, instigation, and inhibition on expectancies of aggressive behavior.

To investigate the role of alcohol expectancy, situational factors, and personality variables in predicting postdrinking aggression, two questionnaire studies were conducted. Subjects were randomly assigned to imagine themselves and their responses in a scenario situation, which was a combination of different beverages (soda vs. alcohol), instigation, and inhibition conditions. Both studies found significant 3-way interactions of personality aggression proneness (Buss-Durkee Hostility Inventory Assault scale) by beverage condition and by situational cue condition on subjects' reported likelihood of engaging in aggressive behavior. Expected aggression was strongly associated with greater aggression proneness in the nonalcoholic condition when there was a situational cue (low inhibition in Study 1, high instigation in Study 2) invoking aggression, but not when the situational cue was absent. This relationship between aggression proneness and expected aggression, however, was attenuated in the alcoholic drink conditions in both studies. In general, it was found that the effect of alcohol on expected aggression was minor relative to the large and significant effects of aggression proneness, instigation, and inhibition.

Effect of religion and religiosity on alcohol use in a college student sample.

Two hundred and sixty-three alcohol using college students completed a questionnaire on their levels of alcohol use, problems with alcohol use, reasons for drinking, perceptions of control over drinking, impulsivity, venturesomeness, irrational beliefs, neuroticism, expectations of alcohol effects, depression, social norms, religious affiliation and intrinsic and extrinsic religiosity. Analyses of variance revealed that students with no religious affiliation reported significantly higher levels of drinking frequency and quantity, getting drunk, celebratory reasons for drinking and perceived drinking norms than those of either Catholic or Protestant religious affiliation, while no significant differences across groups were found for alcohol use problems. Protestants reported significantly higher levels of perceived drinking control than Catholics. Intrinsic religiosity, reflecting one's ego involvement with the tenets of one's religion, appeared to play a more important positive role over drinking behavior for Protestants than for Catholics.

Subchronic inhalation toxicity studies with hydrochlorofluorocarbon 123 (HCFC 123).

Hydrochlorofluorocarbon 123 (HCFC 123) is one of the chemicals being considered as a replacement for the chlorofluorocarbons. Four subchronic inhalation toxicity studies from 1 to 3 months in duration have been conducted with HCFC 123. One study utilized rats and dogs, while the others were limited to rats only. The exposure levels have ranged from 300 ppm up to 20,000 ppm. Although the studies were conducted over a 14-year period, the results were consistent. In all studies, increases in liver weights were seen at 1000 ppm and above; additionally, one showed this effect at 500 ppm. Histopathological findings were minimal, consisting primarily of focal necrosis in the liver of the dogs at 10,000 ppm. Induction of peroxisomal activity, lowering of serum cholesterol and triglyceride levels, and an increase in urinary fluoride levels were also seen. The 4-hr LC50 in the rat has been reported as 35,000 ppm. At 20,000 ppm for 6 hr, the total daily dose on a concentration times time basis is almost equal to the LC50, yet, in the 4-week study, with 20 exposures at this level, there was no mortality or even marked signs of toxicity. There appeared to be no evidence for cumulative toxicity from multiple exposures in these studies. Overall, HCFC 123 appears to have a low level of toxicity by the inhalation route.

A comparative curricular review project.

This article describes a curriculum review project at the Texas College of Osteopathic Medicine. The authors used the Core Curriculum in Osteopathic Education as a standard of comparison of the comprehensiveness of the college's instruction in osteopathic philosophy, principles, and practices and to clarify any differences between the Core Curriculum document and the college curriculum. The process involved a course-by-course search by student physicians and was reviewed by course faculty. Results revealed that the college's coverage was very similar to that proffered by the Core Curriculum. However, there were areas of instructional redundancy, questions of sequencing, and a few topics not addressed within the college curriculum. Thereafter, the faculty consolidated several courses, which produced a net savings of weekly contact hours and allowed further curricular change. Particular attention was given to the manner in which the other courses were scheduled, and, in turn, the consistency and stability of the entire first year was improved significantly.

Acute and neurotoxicity of two structurally related acetylenic compounds: 5,7,11-dodecatriyn-1-ol and 5,7,11,13-octadecatetrayne-1,18-diol.

Two structurally related acetylenic compounds, 5,7,11-Dodecatriyn-1-ol, (Compound A), and 5,7,11,13-Octadecatetrayne-1,18-Diol (Compound B), were evaluated in a tier I toxicology testing program as part of an ongoing research and development program. This battery of acute tests included acute oral, guinea pig maximization, photosensitization, dermal irritation, Ames and multiple genetic endpoint and a 2 week oral fetotoxicity study. Compound A was found to have an oral LD50 of 0.25 ml/kg, be an extreme dermal sensitizer, a mild dermal irritant (PDII of 1.7), and not mutagenic or fetotoxic in the tests employed. Compound B had an oral LD50 greater than 4 g/kg, was a moderate dermal sensitizer and mild dermal irritant (PDII of 1.4), was not mutagenic in the Ames test but weakly increased the incidence of SCEs and gene mutations in Chinese Hamster Ovary cells, and was not fetotoxic. Neither compound was found to be a photosensitizer, but during the course of the photosensitization study Compound A was found to cause neuromuscular signs (including hind limb paralysis) and a bilateral necrosis of the medulla oblongata in female guinea pigs. A similar lesion was found in female rats receiving a single oral dose of 0.25 ml/kg and in nonpregnant females dosed daily for two weeks at 0.03 ml/kg. Compound B was not found to produce any of these neurologic effects.

Inhalation toxicity of hexafluoroisobutylene.

An acute study of hexafluoroisobutylene (HFIB) determined its 4-hr LC50 in rats to be 1425 ppm. In a 2-week study, all animals exposed to 215 ppm for 4 days died or were sacrificed in extremis, while those exposed to the lowest level tested, 53 ppm, showed respiratory and renal effects. Based on the results of these studies, Fischer-344 rats were exposed 6 hr a day, 5 days a week, for 13 weeks to average HFIB concentrations of 3, 10, 30, and 90 ppm. No animals died due to the HFIB exposures. However, at the highest exposure level tested there were numerous marked signs of systemic toxicity in males and females. At all exposure levels, males were more affected than females. The lungs and kidneys were clearly target organs for HFIB, the kidneys being more sensitive in this study (having increased absolute and relative weights, alterations in relevant clinical chemistry parameters, and alterations in microscopic structure). A clear dose-response pattern for the above toxic effects was evident with 10 ppm in the males being an effect level. Male rats exposed to 30 ppm of HFIB had decreased body weights and significantly increased kidney weights. A satellite group of animals was maintained for 2 weeks after the completion of exposure. These animals showed some remission from the observed toxic effects, indicating recovery could be expected in rats from at least most of the toxic effects associated with exposure to HFIB. All effects observed in 3 ppm males disappeared by the end of the recovery period.

Induction and chemotherapeutic response of two transplantable ductal adenocarcinomas of the pancreas in C57BL/6 mice.

Following implant of cotton thread-carrying 3-methyl-cholanthrene into the pancreas tissue of 90 C57BL/6 and 60 BALB/c mice, 13 developed ductal adenocarcinomas. Two of these tumors, both of C57BL/6 origin (Panc 02 and 03), were established in serial s.c. transplant. Panc 02 was treated with 37 different anticancer drugs representing all of the chemical and functional classes of clinically useful anticancer agents including alkylating agents, antimetabolites, agents that bind to or cause scission of DNA, and others that inhibit mitosis or inhibit protein synthesis. When drug treatment was started within 3 to 4 days after tumor implant, Panc 02 showed only limited response to treatment with two nitrosoureas, [N'-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-N-(2-chloroethyl)-N- nitrosourea, monohydrochloride and N-(2-chloroethyl)-N'-(2,6-dioxo-3-piperdinyl)-N-nitrosourea)], and N-phosphonacetyl-L-aspartate. Drug response of Panc 03 was determined only with Adriamycin, 5-fluorouracil, cyclophosphamide, cis-(SP-4-2)-diamminedichloroplatinum, or N,N'-bis(2-chloroethyl)-N-nitrosourea. When drug treatment was started 3 days after tumor implant, high cure rates were obtained with Adriamycin treatment, and limited therapeutic responses were seen to treatment with cis-diamminedichloroplatinum or cyclophosphamide. A comparison of the biological characteristics and drug responsiveness of Panc 02 and Panc 03 with those of a number of other transplantable tumors of mice is reported.

N-nitroso-N-methylurea-induced mammary carcinogenesis: effect of pregnancy on preneoplastic cells.

The effect of pregnancy and lactation on mammary cancers induced with N-nitroso-N-methylurea (NMU) was determined in female outbred Sprague-Dawley rats. The animals received 5 mg NMU/100 g body weight at 50 days of age and were divided into the following groups: virgin, pregnancy (beginning 10 days after NMU administration), pregnancy and lactation (beginning 10 days after NMU), and pregnancy and lactation (beginning 82 days after NMU). The time of appearance of the first palpable cancers was shorter in rats undergoing an early pregnancy. Few cancers, however, were detected from rats after pregnancy or pregnancy and lactation was completed, and a decrease in cancer incidence from virgin rats was observed in these animals at termination of the study. Since NMU is a direct-acting carcinogen with a short half-life, no effect of pregnancy on carcinogen metabolism or binding could have occurred. Preneoplastic cells present before pregnancy appeared to have been either altered (such that their latent period was increased) or destroyed by the hormones associated with pregnancy.

Effect of ovarian hormones on the induction of 1-methyl-1-nitrosourea-induced mammary cancer.

The concomitant administration of 20 micrograms 17 beta-estradiol and 4 mg progesterone/injection (5 days/week) over a 40-day treatment period beginning 10 days after methylnitrosourea (MNU) treatment was as effective as ovariectomy in inhibiting mammary cancers (an 84% reduction from non-hormone treated rats). The primary action of the hormones must have been directed at preneoplastic cells since the hormones were not given until 10 days after MNU (a direct-acting carcinogen with a short half-life).

Mammary carcinogenesis in rats in relation to age at time of N-nitroso-N-methylurea administration.

The effects on mammary carcinogenesis when N-nitroso-N-methylurea (NMU) is administered to rats of different ages were studied. Female outbred Sprague-Dawley rats received two iv injections of NMU (5 mg/100 g body wt/injection) 1 week apart beginning at either 35, 50, 80, 140, or 200 days of age. Animals were killed 6 months after the initial NMU injection, and all mammary tumors were histologically classified. The percent incidence of mammary carcinomas for each age group was as follows: 100%, 35 days old; 94%, 80 days old; 59%, 80 days old; 30%, 140 days old; and 22%, 200 days old. Rats receiving NMU at a young age also exhibited a greater number of carcinomas per rat with latent periods that were in general shorter than those of rats treated at later ages. Since NMU does not require metabolic activation, the observed decrease in chemically induced mammary tumors in aging rats appears to be primarily due to changes occurring within the mammary gland.